Biologic laws governing functions of muscles that move the mandible. Part III. Speed of closure--manipulation of the mandible. The character of the occlusal surfaces of teeth programs the functions of muscles that move the mandible and imposes specifications upon the dentist within which he must work in manipulating the patient's mandible. If he exceeds those specifications, protective responses that inhibit his efforts are elicited in the patient's musculature. A knowledge of the laws governing functions of the muscles that move the mandible enables the dentist to acquire mandibular-manipulation skills necessary for diagnosis and effective occlusal treatment. A model in which the dentist visualizes the patient, the patient's protective reflexes, the components of the patient's gnathostomatic system, and himself as four independent personalities participating in the jaw manipulation is a useful tool in acquiring mandibular-manipulation skills. This article is Part III of a series presented in four parts on the "Biologic Laws Governing Functions of Muscles That Move the Mandible."


Characteristics of temporomandibular joint problems. A review of the characteristics of 145 patients with temporomandibular joint and myofascial pain-dysfunction syndrome is presented. The material includes both temporomandibular and myofascial involvements. The evidence supports the psychophysiologic etiology theory for most patients. This does not exclude anatomic abnormalities which may be present in such patients nor anatomic abnormalities which may be present without psychogenic causes. The lack of awareness of the range of condylar movement is contributory to iatrogenic trauma. A classification of etiologic factors is proposed. The superimposition of one upon another can create a severe problem. The superimposition of two upon a third can create an unusually severe problem.


Laser holography in dentistry.

Laser holography in dentistry.


Temporomandibular joint function and its effects on concepts of occlusion.


Effects of supervised daily dental plaque removal by children: II. 24 months' results. After two school years of a supervised daily plaque-removal program in school, children in the treatment group showed a significant reduction in plaque and gingival inflammation scores compared with children in the control group. However, differences between groups in terms of plaque and gingivitis scores virtually disappeared during the summer vacation. The increment of dental caries was lower in the treatment group than in the control group, but the reduction, which averaged about 20 percent, was not statistically significant either for teeth or for surfaces. Although the 24-month findings of the present study indicate some degree of success in reducing plaque and gingivitis and a marginal effect in reducing the incidence of dental caries among children who engaged in daily, supervised plaque-removal in school, obvious drawbacks limit the value of this regimen.


A statistical model of changes in locations of primary-care dentists in a rural state.


Expenditures for the dental care of indigent children in the Chattanooga project, 1971-1975. This paper is part of a continuing study of the cost of children's dental care in a publicly funded model program. The Program--the Chattanooga Project--was designed to provide information and experience necessary for the development of similar programs elsewhere in the United States. From 1970 to 1975 comprehensive dental care was provided, at no charge, to an average of 5,500 indigent children per year. Children were treated in private practices (39%), public fixed clinics (20%), and public mobile clinics (41%). Costs were defined as public expenditures for purchasing care from private practitioners or producing care in public practices. As a framework for the analysis, program activities and their respective costs were divided into direct and indirect components. The former relate to the provision of care and the latter to noncare-oriented activities. Direct (indirect) costs per patient were $46.56 ($16.31) in private practices, $40.17 ($16.11) in fixed clinics, and $35.49 ($13.41) in mobile clinics. These results substantiate previous findings from a shorter period. A priori reasons for differences among the three modes in terms of patients' health status or the type of care provided have been specified and are currently under investigation.


The cost of providing restorative dentistry in an alternative delivery mode. This study is based on the Forsyth Dental School experiment, where it was shown that dental hygienists can be trained to perform restorative dental functions which are now the exclusive responsibility of dentists. The focus of the Forsyth study was to determine the length of training time required and to measure the qualitative and quantitative aspects of services carried out by the hygienists. As a follow-up to that study, this paper is concerned with the economic aspects of the personnel substitution suggested by the Forsyth project. The basic hypothesis of the study is that there would be a considerable gain from this change, and that this gain can be measured by estimating the costs of operation in the new setting anc comparing them to costs in the conventional setting. Combining estimated clinic costs and productivity data provides a measure of the per-surface supply price for an amalgam restoration. This estimate is 44 percent lower than usual fees and 29 percent lower than current welfare fees. The magnitude of this difference implies that the introduction of Forsyth clinics would lead to considerable economics in the elivery of these services.


Some random musings about quality.

Some random musings about quality.


Some bicentennial reflection for century III.


Fluorescein angiography of the retina.

Fluorescein angiography of the retina.


Medical termination of midtrimster pregnancy in a community hospital. 181 cases of patients (aged 12-43) who underwent a second trimester abortion (14-20 weeks gestation) by intraamniotic hypertonic saline or prostaglandin F2 alpha are presented for the purpose of evaluating methodologies.  61 patients had hypertonic saline infusion, 37 with Laminaria tents inserted and 24 without.  1 of the 24 cases represents a method failure which was completed surgically 2 days after infusion.  Of the 37 patients treated with saline and Laminaria tent, there were no method failures.  122 patients had a prostaglandin infusion and Laminaria tent insertion, and 22 also had intraamniotic calcium gluconate.  The 22 cases who received an intraamniotic prostaglandin and calcium infusion with a Laminaria tent had no failures.  The prostaglandin group demonstrated a shorter infusion-abortion time (average, 17 hours).  When calcium was added to prostaglandin, no potentiating effect was noted.  Major complications, most notably retained placenta, were noted with the saline method.  Prostaglandin proved the most effective and least risky procedure.


The triple-bite single-suture technique for correction of urinary stress incontinence.


Program for risk factor modification and selective screening for ostensibly healthy adults.


Endotracheal intubation in acute laryngotracheobronchitis.


Intestinal hemangioma with intusssception in infancy.


Public opinion about medical care and health education.


President's message. Blue ribbon committee appointed.


Dental practice management and taxes.

Dental practice management and taxes.


Behavior modification in the management of obesity.


The current diagnosis and treatment of renal injury.


Some thoughts about the profession of medicine.


Can the profession of medicine survive?

Can the profession of medicine survive?


Medical evaluation of the high risk driver.


Sex influences on attitudes during hospitalization.


"Death with dignity" legislation in South Carolina: an appraisal.


Lead poisoning in South Carolina.

Lead poisoning in South Carolina.


The fetal alcohol syndrome.

The fetal alcohol syndrome.


Current status of halothane hepatitis.

Current status of halothane hepatitis.


Medical education today.

Medical education today.


The South Carolina physician as an expert witness--enforced charity or for a reasonable fee?


Perinatal mortality in South Carolina: analysis with linked birth and death certificates.


General impressions of overall tour.

General impressions of overall tour.


A dental wife's viewpoint: people-to-people tour of Eastern and Western Europe.


People-to-people tour of four Iron Curtain countries.


Dental impressions from Russia. A summary of conversations and observations from three Russian Dental Institutions.


Impressions!!

Impressions!!


Histopathological study of regional lymph nodes in osteosarcoma. This paper presents the histological appearance of the lymph nodes in cases of osteogenic sarcoma of the limb bones. The nodes were studied for the degree of sinus histiocytosis. Cases with no sinus histiocytosis showed a poor prognosis while cases with moderate to marked sinus histiocytosis showed a better rate of survival. Since the regional lymph nodes play an important part in the immunological process, preservation of regional nodes is suggested.


Presidental perspective. Is there a solution to denturism?


Paget's sarcoma in Tasmania.

Paget's sarcoma in Tasmania. Six proven cases of Paget's sarcoma occurred in Tasmania in the decade 1965 to 1974. The incidence was 0-16 cases per 100,000 population per year. The sex ratio was two male: one female. The average age was 61-2 years. All cases occurred in the pelvis or adjacent femur. Average time of survival after onset of symptoms was one year. Two patients had lymph node metastases. One patient had no pulmonary metastases; a further patient may have had no pulmonary metastases. All patients were born in Australia (State of Tasmania) of predominantly Anglo-Saxon stock.


Sounding board. The Frankenstein Factor.


n-Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells.


Use of Ficoll-sodium metrizoate density gradient to separate human X-and Y-bearing spermatozoa.


The trauma victim: priorities of management.


Efficacy of slow injection of diazoxide in accelerated hypertension.


Traumatic bowing of the radius and ulna in children.


Planimetric evaluation and comparison of roentgenograms of osteogenic sarcomas induced by 226Ra and 224Ra in mice. Osteosarcomas were induced in mice by three activities of 226Ra (8.8 micronCi, 24.6 micronC and 70.5 micron Ci/kg) and by three activity levels of 224Ra administered in fractionated doses during a period of 75 weeks (total activity per mouse: 0.65 micron Ci, 1.88 micron Ci). In the 226Ra series 74 cases and in the 224Ra series 89 cases of osteosarcomas were evaluated by means of planimetric measurements of roentgenographic images, including the calcified structures. Even though it is not possible to differentiate the series precisely, still some differences between tumors under study could be found. In comparison with 226Ra series, the sarcomas induced by 224Ra are in average rather larger, calcified stuctures appear not to be fully developed and differentiated, he anatomical distribution is different from that characteristic to the 226Ra induced tumors, the mean life span is shorter. It is quite likely that not only the incidence but also some of the features of osteosarcomas are dependent on the time and tissue distribution of the dose delivered.


Nephrotoxicity associated with combined gentamicin-amphotericin B therapy. The administration of a low total dose of amphotericin B to four consecutive patients already receiving gentamicin resulted in a deterioration of renal function in all. No other cause of the renal dysfunction was apparent in three cases. It appears probable that these drugs exhibit synergistic nephrotoxicity.


Animal model for multiple sclerosis. Chronic experimental allergic encephalomyelitis in inbred guinea pigs.


Immunology of atrophic gastritis.

Immunology of atrophic gastritis.


Silent mitral stenosis with atrial fibrillation. Detected by echocardiography.


Ultrasonography of acute medical emergency.


Influenza. Surveillance report for "swine flu" scare year 1976.


Breast reconstruction following mastectomy.


The psychiatrist and the nursing home.

The psychiatrist and the nursing home.


Occupationally related emotional problems.


Clinicopathologic conference. Obstructive jaundice. Case presentation.


Detection, evaluation, and treatment of high blood pressure.


Death associated with dantrolene sodium.


Hypercalcemia complicating vulvar carcinoma.


Simultaneous intrauterine and extrauterine pregnancies.


Metastatic breast cancer. Pelvic and abdominal complications.


Sclerosing mediastinitis. Presumed to be due to primary aspergillosis.


Typhoid fever in pregnancy with probable typhoid hepatitis.


Detoxification of alcoholic patients in acute-care hospital. Outline of effective short-term program.


Immunizations for children. Issues and recommendations.


Communicable disease reporting.

Communicable disease reporting.


Continuing education for community pharmacist. Medical school program.


Bureaucratic aggrandizement: a threat to "advanced planning".


The dentist's role and responsibility under group dental care programs. Part II (of a series).


A response to "the value of TEAM".

A response to "the value of TEAM".


[Self-criticism, too].

[Self-criticism, too].


The need for forensic odontology. A case in point: Eastern Airlines Flight 66.


The psychologically handicapped odontophobe.


Dentistry and the aphasic patient.

Dentistry and the aphasic patient.


Confirmations are a waste of time.

Confirmations are a waste of time.


Danger lurks in the medicine bottle.

Danger lurks in the medicine bottle.


The S.D.S. should be proud.

The S.D.S. should be proud.


The dentist's role and responsibility under group dental care programs. Part III (of a series).


The ADA conference on increasing access to dental care. A report.


The value of TEAM in New York state.

The value of TEAM in New York state.


The root canal game.

The root canal game.


[A challenge: the profession and the dental students].


Gnathological considerations of a controversial nature.


The legal story. The first amendment: interpretations.


Time for review.

Time for review.


Retinoblastoma and osteogenic sarcoma.

Retinoblastoma and osteogenic sarcoma. Radiogenic and non-radiogenic osteosarcomas are rather frequent in retinoblastoma patients and probably also in retinoblastoma families. Besides the pathologic gene for retinoblastoma, there must be a predisposition to develop osteogenic sarcomas, which is probably genetic.


Medical-legal aspects of dental radiology in personal injury cases.


Good bookkeeping breeds good business.

Good bookkeeping breeds good business.


What's your diagnosis, doctor?

What's your diagnosis, doctor?


X-rays for orthodontic purposes.

X-rays for orthodontic purposes.


Dental implantation.

Dental implantation.


Analysis of five years of study of vitreous carbon endosseous implants in humans.


The subperiosteal implant denture program at the University of Southern California. Part I, introduction and implant denture removal.


A new modification in the ramus frame.

A new modification in the ramus frame.


Periodontal aspects of implants.

Periodontal aspects of implants.


Dental implants, periodontal disease and nutrition.


Relating temporomandibular joint dysfunction and occlusal imbalance to implant dentistry.


The R2S(5) and sliding cable/coping systems of implantation.


Cephalic kinetics of intra-arterially injected lidocaine. The intravenous injection of 3 mg./kg. of lidocaine into the facial artery resulted in internal carotid artery blood levels between 5 and 7 microgram/ml. 15 seconds thereafter. Internal and external jugular vein blood levels exceeded 30 microgram/ml. at the same time. When the same amount of lidocaine was injected into the facial vein, carotid blood levels were less than 3 microgram/ml., peaking at 30 seconds. Concentrations of the local anesthetics in the jugular vein peaked at 15 seconds, exceeding 35 microgram/ml. The feasibility of local anesthetic drugs reaching the cerebral circulation through a retrograde pathway was indicated, suggesting that this mechanism may be the route for some of the untoward reactions observed after the injection of local anesthetics in the head and neck area.


Vestibular extension with xenogenous fascial grafts. Fascia obtained from the abdominal wall of a rat was transplanted to the oral cavity of five dogs as a graft material for vestibular extension. In all five dogs the grafted fascia remained in place as the surgical defects were covered with epithelium, which transpired within a period of 4 weeks. After 6 months, the vestibular depth was increased significantly and the vestibule was smooth and regular.


Biopsy technique for fibro-osseous and osteolytic lesions of the jaws. A biopsy technique is presented for obtaining small tissue samples from fibro-osseous and osteolytic lesions which are not readily accessible for surgical biopsy. Trephine burs and a nonaspirating biopsy needle may be utilized for obtaining adequate tissue from fibro-osseous and osteolytic lesions for frozen section and routine histopathologic examination.


Garré's osteomyelitis of the mandible. Report of a case. A case of Garré's disease has been reported. This case is atypical in that the patient presented with only a periosteal bone mass and a negative history of toothache, abscess, or trauma to the area. Because of this, diagnosis was not possible without microscopic examination. Atypical cases of this nature cause diagnostic problems, and several disease states must be considered in a differential diagnosis. These include the following: 1. Ewing's sarcoma, which also occurs in this age group and may show cortical reduplication on radiographic examination. The prognosis in cases of Ewing's sarcoma is poor, and death may occur in a matter of weeks. 2. Infantile cortical hyperostosis (Caffey's disease), which is characterized by development of soft-tissue swelling and cortical thickening of the mandible. The disease runs a benign course and regresses without treatment. 3. Osteogenic sarcoma, which occurs in slightly older age groups but presents as a cortical expansion with facial deformity. The disease is highly malignant and carries a poor prognosis.


The incidence and relationship of the lateral ramus prominence to the mandibular foramen. A study was undertaken to determine the incidence of the lateral ramus prominence and its relationship to the mandibular foramen. The lateral ramus prominence, as determined by inspection and palpation, was identified on both the right and left rami of all specimens. Bilateral measurements were made on fifty randomly selected adult dentulous mandibles. Significant correlation coefficients were obtained for all measurements between right and left rami. Therefore, either the left or right side measurement for each parameter was selected at random, and the data were subjected to statistical analysis. The lateral ramus prominence varied from 4.7 mm. anterior to 4.7 mm. posterior to the foramen, and from 0.9 mm. to 16.2 mm. superior to the foramen. It was located anterior to the foramen 66 per cent of the time.


Vitamin E and periodontitis in the rat.

Vitamin E and periodontitis in the rat. This investigation was designed to study the effect of vitamin E on the course of periodontitis in thirty-six adult male albino rats. The rats were divided into three groups of twelve and placed on test diets which consisted of pelleted feed that either was deficient in, or contained adequate and high amounts of, vitamin E. After the animals had been on their respective diets for 8 weeks, a local irritant in the form of a stainless steel wire was placed around the maxillary left second molar of each animal. The wire served both as a mechanical irritant and as a collector of plaque and debris. Six weeks after the wire was placed, the animals were killed and the periodontium was examined histologically. Migration of the epithelial attachment, alveolar bone level, and numbers of inflammatory round cells were then evaluated on both sides of the maxilla. Multivariate analysis of variance was used to determine significant difference in the parameters. The results of this experiment indicate that a deficiency of vitamin E does not cause increased destruction of the periodontium in the presence of periodontitis. Moreover, no beneficial effects from the therapeutic use of vitamin E to combat periodontitis were found.


The oral melanotic macule.

The oral melanotic macule. A clinical and histologic study of eighty oral melanotic lesions which do not readily fit into recognized categories of melanotic lesions was conducted. These lesions tend to occur in the fifth decade of life and are most frequently seen on the gingiva, with the buccal mucosa and palate the next most frequent sites. The lesions are usually single, smaller than 1 cm., but they may also occur as multiple lesions. There is no sex bias, and there seems to be a number of etiologic factors. In a few cases long-term follow-up was possible. There is no indication of a tendency toward recurrence or development of malignant lesions. Histologically, none of the lesions shows atypia. Melanin pigmentation tends to be present in significant amounts in the basal-cell layer and less often in the lamina propria. There are no outstanding histologic differences among the eighty specimens. It is suggested that the term oral melanotic macule be used for these lesions, unless a specific cause can be confirmed by clinical data. Although these lesions should not be considered premalignant, it would be prudent to remove them for histologic confirmation of clinical impressions.


Histopathologic, ultrastructural, and immunologic findings in an oral psoriatic lesion. There has been some controversy over whether psoriasis can involve the oral mucosa. An oral lesion in a 32-year-old man with a psoriatic scalp lesion has been studied by light and electron microscopy and by immunologic methods. Results from each of these three techniques are consistent with previous findings in psoriatic lesions and suggest that oral psoriasis can occur.


Sebaceous choristoma of the thyroglossal duct. The presence of sebaceous glands within the oral mucosa is not uncommon. Such Fordyce granules are frequently seen on the buccal mucosa and lips, as well as in the retromolar area, gingiva, and palate. Whereas sebaceous elements are rarely encountered on the tongue, three cases of ectopic sebaceous glands have been reported in association with apparently patent thyroglossal ducts. An interesting case of a previously unreported sebaceous choristoma of the thyroglossal duct is described.


Intraoral melanocytic cellular nevi.

Intraoral melanocytic cellular nevi. Eight cases of intraoral melanocytic cellular nevi are presented, together with the clinical features and limited follow-up information. These cases are added to those already published, so that a meaningful series may eventually be analyzed.


Taurodontism, short roots, and external resorption, associated with short stature and a small head. This article describes a patient who exhibited taurodontism, relatively short roots, external resorption of the roots of the anterior teeth, and a marked tendency toward microcephalic dwarfism. This case is similar to that reported previously by Sauk and Delaney.


Squamous-cell carcinoma in a residual mandibular cyst. Described is a case of squamous-cell carcinoma arising in a residual cyst in a 60-year-old edentulous woman. The clinical and radiographic diagnosis was residual cyst, and the treatment employed was conservative surgical enucleation. The cause of these changes is unknown. Theoretically, the inflammatory reaction may have been a predisposing factor.


Villonodular synovitis with synovial chondromatosis. Pigmented villonodular synovitis and synovial chondromatosis are uncommon benign lesions involving the articular surfaces of diarthrodial joints. Reported is a case of a benign synovial lesion of the temporomandibular joint, which was clinically thought to be a malignant parotid compartment tumor, showing histologic features of both pigmented villonodular synovitis and synovial chondromatosis. A review of the literature reveals a single case in which cartilaginous bodies were found in the joint; however, the synovial tissue showed features of only villonodular synovitis, with no mention of cartilaginous foci.


Simple metallic compounds as pulp-capping agents. A pilot study. A pilot study is described in which the exposed pulps of molar teeth of normal laboratory rats were capped with various metallic compounds in general medical usage. There appeared to be no relationship between the response obtained and the pH of the compounds studied. Aluminum powder, aluminum hydroxide, Aludrox, aluminum oxide, light magnesium oxide, magnesium hydroxide, and titanium dioxide gave poor results. Barium sulfate, calcium carbonate, cupric oxide, ferric oxide, heavy magnesium oxide, and stannic oxide merited more detailed study.


Polyethylene tubes as a model for the root canal. Polyethylene tubes, closed at both ends with casting wax and with four perforations in the middle, were implanted subcutaneously in rats and evaluated as a research model simulating the root canal. As controls, wax bars and unperforated tubes were implanted. Attention was given to the reaction of the tissue surrounding the perforated empty tube, the tissue reaction to polyethylene and casting wax, and to the displacement of the tubes.


Effectiveness of root canal irrigation.

Effectiveness of root canal irrigation. When root canals are being enlarged, repeated irrigation is mandatory. Under the conditions of this study, the most significant factor in obtaining maximum results in root canal irrigation is the diameter of the canals. The removal of debris seems to be a function of canal diameter rather than the type of solution used.


Radiation exposure and distribution measurements for three panoramic x-ray machines. 1. Exposures to internal sites in the phantom varied as follows: Panorex, 0.3 mr to 2.4 r; Orthopantomography, 0.4 mr to 0.8 r; Panelipse, 0.2 mr to 1.4 r. 2. With the phantom exposed for a normal-density radiograph at 65 KVP, the average radiation exposure at the sites measured were for the Panorex, Orthopantomograph, and Panelipse respectively: 8, 13, and 4 mr at the pituitary gland; 22, 62, and 8 mr at the superior area of the parotid gland; 13, 8, and 5 mr at the thyroid gland; 343, 425, and 365 mr at the submaxillary gland; and 50, 154, and 272 mr at the base of the tongue. 3. External exposures to the phantom and patients were found to be in good agreement at the low KVP. At the high KVP (using patients who were larger than the phantom), exposures at lateral and posterior sites showed relatively good agreement between phantom and patients, while exposures at anterior sites were less in patients. 4. The average stray radiation measurement at 1 meter from the phantom during pantomography with the three machines was 0.125 mr per exposure cycle. Individual averages were: Panorex, 0.10 mr; Orthopantomograph, 0.13 mr; and Panelipse, 0.15 mr.


New device to quantitate alveolar bone loss. The advantages of the device described here are that (1) it produces sharp grid outlines on the film that can be accurately measured, (2) distortion factors can be compensated so that an accurate measurement can be obtained of any bony changes, and (3) the patient is exposed to radiation only once and two films are produced with and without the grid.


Retrieval of broken instrument from root canal.


Duplication of the submandibular salivary duct.


On viral infectivity and carcinogenesis.


Thalassemia terminating in erythremic myelosis.


The happy patient.

The happy patient.


From the secretary's desk.

From the secretary's desk.


President's message.

President's message.


Is Juarez doomed?

Is Juarez doomed?


Dental prepayment: friend or foe?

Dental prepayment: friend or foe?


Exeperimental studies on clinical aspects of composite resins.


Government's attacks on the professions.


Minnesota's pilot dental care program for senior citizens.


Arrangement of water molecules in cavities and channels of the lattice of [Phe4Val6]antamanide dodecahydrate. The synthetic, biologically active, [Phe4Val6] analog of natural antamanide has been crystallized from a solution containing calcium nitrate, acetone, and acetonitrile. The crystal does not contain any Ca2+ ions but does contain 12 water molecules per peptide molecule. The conformation of this dodecahydrate is identical to the trihydrate crystallized from n-hexane/methyl acetate. The packing in both crystals is very similar, governed by parallel bands of phenyl and pyrrolidine ring stacking and by continuous channels for the solvement molecules, water in this case and n-hexane/methyl acetate in the previous study. The two structures are not ideally isomorphous, since the c cell parameter differs by more than 1.0 A in the two cells. There are three functions for H2O molecules: the three intrinsic H2O molecules in the interior of the peptide ring, the H2O bound to the exposed C=O groups, and the H2O molecules that fill space in the solvent channels. There are no direct hydrogen bonds between neighboring peptide molecules and there are only two intramolecular NH-O=C bonds (of the 5 leads to 1 type).


The buccal bitewing radiograph for the child patient.


Magnetic properties and structure of oxyhemoglobin. A review of the published evidence reinforces the conclusion reached by Pauling and Coryell in 1936 (Proc. Natl. Acad. Sci. USA 22, 210-216) that oxyhemoglobin in blood or in solution at 20 degrees has zero magnetic moment and fails to support a recent contradictory suggestion based on magnetic susceptibility of frozen samples at temperatures below 250 K. Predicted values of bond lengths and bound angles for carbonmonoxyhemoglobin and oxyhemoglobin are given.


Health legislation: make your voice heard.


Kinetics of hemoglobin-carbon monoxide reactions measured with a superconducting magnetometer: a new method for fast reactions in solution. A new technique for measuring fast reactions in solution has been demonstrated. The changes in magnetic susceptibility during the recombination reaction of human hemoglobin with carbon monoxide after flash photolysis have been measured with a new high-sensitivity instrument using cryogenic technology. The rate constants determined at 20 degrees (pH 7.3) are in excellent agreement with those obtained by photometric techniques [Gray, R.D. (1974) J. Biol. Chem. 249, 2879-2885]. A unique capability of this new method is the determination of the magnetic susceptibilities of short-lived reaction intermediates. The magnetic moment of the intermediate species Hb4(CO)3 was found to be 4.9+/-0.1 muB in 0.1 M phosphate buffer by partial photolysis experiments. This value agrees with the predictions of two-state allosteric models of cooperativity in hemoglobin. Possible applications and improvements in this technique are discussed.


Structures of enzyme-substrate complexes of lysozyme. Conformational energy calculations were used to determine the binding structures of two oligosaccharides (GlcNAc)(n), in which n = 5 and 6, in the rigid active site of lysozyme (mucopeptide N-acetylmuramoylhydrolase, EC 3.2.1.17). Starting with the lowest energy binding structures of (GlcNAc)(4) as determined in a previous publication, we added a fifth GlcNAc residue to this tetramer in three different conformations, corresponding to the left-handed and right-handed helical structures and an intermediate structure, and the energy of each complex was minimized. The most stable binding conformation of the fifth residue of the pentamer was closest to the left-handed helical one. During energy minimization, the fourth residue of the pentamer moved from its initial position near the surface of the active site farther into the active site cleft at binding site D. Binding structures of (GlcNAc)(6) were then examined by addition of a residue to the lowest energy structure of (GlcNAc)(5), and it was found that the sixth residue of the hexamer binds in a conformation again close to the left-handed helical one. Stable binding regions of the rigid active site for the fifth and sixth residues were found to be near arginyl 45 and asparaginyl 46, on the opposite side of the active site cleft from arginyl 114. When the calculated structure of the lysozyme-(GlcNAc)(4) complex (used here as the starting structure for addition of the fifth and sixth residues) is compared with recent experimental data, it is found that the calculated structure is a reasonable one. Of all binding regions available to the saccharide residues, the C site binds GlcNAc with the lowest energy, in agreement with experiments.


Sequence specificity of mutagen-nucleic acid complexes in solution: intercalation and mutagen-base pair overlap geometries for proflavine binding to dC-dC-dG-dG and dG-dG-dC-dC self-complementary duplexes. The complex formed between the mutagen proflavine and the dC-dC-dG-dG and dG-dG-dC-dC self-complementary tetranucleotide duplexes has been monitored by proton high resolution nuclear magnetic resonance spectroscopy in 0.1 M phosphate solution at high nucleotide/drug ratios. The large upfield shifts (0.5 to 0.85 ppm) observed at all the proflavine ring nonexchangeable protons on complex formation are consistent with intercalation of the mutagen between base pairs of the tetranucleotide duplex. We have proposed an approximate overlap geometry between the proflavine ring and nearest neighbor base pairs at the intercalation site from a comparison between experimental shifts and those calculated for various stacking orientations. We have compared the binding of actinomycin D, propidium diiodide, and proflavine to self-complementary tetranucleotide sequences dC-dC-dG-dG and dG-dG-dC-dC by UV absorbance changes in the drug bands between 400 and 500 nm. Actinomycin D exhibits a pronounced specificity for sequences with dG-dC sites (dG-dG-dC-dC), while propidium diiodide and proflavine exhibit a specificity for sequences with dC-dG sites (dC-dC-dG-dG). Actinomycin D binds more strongly than propidium diiodide and proflavine to dC-dG-dC-dG (contains dC-dG and dG-dC binding sites), indicative of the additional stabilization from hydrogen bonding and hydrophobic interactions between the pentapeptide lactone rings of actinomycin D and the base pair edges and sugar-phosphate backbone of the tetranucleotide duplex.


Ultraviolet resonant Raman spectroscopy of nucleic acid components. The first resonant Raman excitation profile using UV as well as visible radiation is presented. Measurements of the intensity of the Raman spectrum of adenosine 5'-monophosphate as a function of the frequency of the incident laser light are presented in the range from 20 to 38 kK (1000 cm-1). The scattering intensity per molecule increases by about 10(5) as the laser is tuned from low to high frequencies. The Raman excitation profile has been calculated by using a simple form of the vibronic theory of Raman scattering. The theoretical curves are found to adequately fit the data using only the frequencies of the excited electronic states of AMP and their corresponding vibronic linewidths as adjustable parameters. The Raman bands at 1484 cm-1 and 1583 cm-1 appear to obtain virtually all of their intensity from a weak electronic transition at 276 nm. The set of Raman bands in the range 1300 cm-1-1400 cm-1 appear to derive at least part of their intensity from an electronic band whose 0-0 transition is in the 269-259 nm region although the possibility of some intensity arising from the vibronic mixing between these two electronic states cannot as yet be ruled out.


Molecular properties of the nerve growth factor secreted in mouse saliva. Some molecular properties of the nerve growth factor (NGF) secreted in mouse saliva and that present in submandibular glands have been measured for comparison with previously studied forms of NGF. The results show that mouse saliva contains two biologically active NGF species. One has a molecular weight near 114,000, and the other, a molecular weight of 13,000. The larger form is being continuously degraded to yield the smaller one, probably as a result of a slow enzymatic process. Virtually identical results were obtained with crude submandibular gland extracts. The larger NGF is neither the well-known 7S NGF nor 2.5S NGF. Our results indicate that the larger salivary NGF is the naturally occurring form of NGF as it exists in the submandibular gland and as it is secreted in saliva. Its biological properties and its function in saliva, if any, remain to be elucidated.


A site-specific single-strand endonuclease from the eukaryote Chlamydomonas. We have found a unique deoxyribonuclease in extracts of the eukaryotic green alga Chlamydomonas. When incubated with viral DNA from adenovirus-2, this enzyme produces discrete fragments that form bands upon electrophoresis in an agarose gel. Site specificity of the enzymatic cleavage examined by identifying the 5'-terminal nucleotides in cleaved adenovirus-2 DNA and by studies with synthetic polynucleotides of defined sequence, indicates that the initial endonucleolytic cleavage occurs at a site containing a deoxythymidine residue. Electron microscopy of cleaved adenovirus-2 DNA revealed single-strand segments within duplex DNA. We propose that the enzyme acts by making initial site-specific single-strand incisions, followed by subsequent excision on the same strand, producing a gapped duplex molecule; and that double-strand scissions result from limited occurrence of overlapping single-strand gaps on complementary strands.


Loss of infectivity of brome mosaic virus RNA after chemical modification of the 3' or 5' terminus. Brome mosaic virus (BMV) RNA that had both termini chemically modified by periodate oxidation and aniline-catalyzed cleavage of the terminal nucleotide had drastically reduced infectivity. BMV RNA that was first enzymatically tyrosylated to protect the 3' terminus from modification, and then modified at the 5' terminus by periodate oxidation and aniline cleavage, had a similar reduction in infectivity. Tyrosylation followed by acetylation modifies only the 3' terminus. Nevertheless, acetylated tyrosyl-BMV RNA was less than one-fourth as infectious as a control sample subjected to procedures that differed only by the presence of tyrosinol (which prevents aminoacylation and subsequent acetylation). For each modified form of viral RNA, care was taken to test the infectivity of appropriate control samples. The integrity of the modified RNAs was examined by gel electrophoresis and by biological translation and aminoacylation assays. We conclude that, in different ways, both the 5'- and 3'-terminal structures of BMV RNA play important roles during infection of the host.


Biotinylinsulins as potential tools for receptor studies. The preparation of affinity columns that contain insulin attached to Sepharose in a targeted manner by way of biotin-avidin noncovalent bonds is described. Insulin was acylated selectively at the amino terminus of the B chain with the N-hydroxysuccinimido ester of biotin to form N(alpha,B1)-biotinylinsulin. The ability of this modified insulin to stimulate rat epididymal adipocytes was (mean +/- SD) 94 +/- 9.6% (P, 0.05) that of the control insulin. N(alpha,B1)-Biotinylinsulin displaced 4-hydroxyazobenzene-2'-carboxylic acid from avidin, demonstrating affinity for this protein. The formation of the N(alpha,B1)-biotinylinsulin-avidin complex was visualized by cellulose acetate electrophoresis at pH 4. N(alpha,B1)-Biotinylinsulin combined with avidin attached to Sepharose to form affinity columns in which the hormone was attached to the support by strong noncovalent bonds. The determination of the loading of avidin-Sepharose columns with biotinylinsulin was greatly facilitated by the attached biotin which provided a marker whose concentration could be assessed accurately by titration with avidin. Biotinylinsulin attached to avidin-Sepharose beads retained the ability to stimulate rat epididymal adipocytes. The activity of several samples of these beads was about 15% that of free biotinylinsulin, based on the amount of biotinylinsulin anchored to the support. The advantages of biotinylated hormones for the targeted attachment of hormones to solid supports are discussed.


Interaction between the third complement protein and cell surface macromolecules. The activated form of the third complement protein, C3b, forms a stable complex with components of plasma membranes and particulate entities such as zymosan. The complex resists the action of detergents and protein denaturants as well as extremes of temperature, salt concentration, and pH. It can, however, be broken by exposure to hydroxylamine or by ammonolysis followed by incubation with sodium dodecyl sulfate. Thus, the complex appears to result from a hydrophobic interaction as well as a bond susceptible to nucleophilic attack.


A DNA fragment containing the origin of replication of the Escherichia coli chromosome. A 38 kilobase pair region of the Escherichia coli K12 chromosome containing the replication origin has been physically mapped with restriction endonucleases EcoRI and HindIII. Replication starts within or very near a 1.3 kilobase pair HindIII fragment in the middle of this region and proceeds outward in both directions with apparently equal speed. This pattern was observed in both dnaA and dnaC temperature-sensitive (ts) initiation mutants at the start of the synchronous round of replication which occurs after downshift from the nonpermissive to the permissive temperature.


Distribution of 5-methylcytosine in chromatin. The content of 5-methylcytosine in eukaryotic DNA was measured by mass spectrometry. Almost equal amounts of methylated cytosine were found in the DNA of various tissues of the chicken. When chromatin or nuclei were digested with micrococcal nuclease, 50% of the DNA was found to be nuclease resistant. In contrast to this, over 75% of the 5-methylcytosine was protected from nuclease digestion by chromatin proteins. These results suggest that 5-methylcytosine is nonrandomly distributed with respect to the nucleoproteins.


Enzymes as reagents in peptide synthesis: enzyme-labile protection for carboxyl groups. N-Benzyloxycarbonyl derivatives of isoglutamine and isoasparagine were coupled with arginine methyl ester through the action of dicyclohexylcarbodiimide. The resulting benzyloxycarbonyl derivatives of isoglutaminylarginine methyl ester and isoasparaginylarginine methyl ester were treated with trypsin for removal of the ester groups and then with porcine pancreatic carboxypeptidase B for liberation of arginine and the original benzyloxycarbonyl derivatives of isoglutamine and isoasparagine. This scheme represents a reversible masking of the side-chain carboxyl functions of aspartic and glutamic acid residues. Possible applications of esters and amides of arginine as reversible blocking groups in protein semi-synthesis are discussed along with prospects and strategies for developing related techniques of higher efficiency.


Glycophorin and the concanavalin A receptor of human erythrocytes: their receptor function in lipid bilayers. Two integral glycoproteins from the human erythrocyte have been studied after their incorporation into lipid bilayer systems. Glycophorin (which is the M/N blood group determinant) and the concanavalin A receptor were isolated and purified prior to incorporation into model membranes by dialytic removal of detergent from lipid/protein solutions. Under the conditions described, glycoprotein receptors maintain their function in that they bind external agents specific for them, such as concanavalin A and immunoglobulins. So-called intramembranous particles are a feature of freeze-fractured preparations of lipid bilayers containing either (or both) glycoprotein(s), and to some extent each has a characteristic particle appearance. Liposomes containing the concanavalin A receptor (with or without glycophorin) are agglutinable by concanavalin A, whereas human erythrocytes are normally considered to be nonagglutinable by this lectin. Liposomes containing glycophorin alone are readily agglutinable by the appropriate glycophorin-directed M/N antiserum, as are human erythrocytes. The added presence of concanavalin A receptor in the liposomes can markedly inhibit agglutination by M/N antiserum without preventing immunoglobulin binding.


Superiority of interconvertible enzyme cascades in metabolic regulation: analysis of monocyclic systems. A theoretical analysis of monocyclic cascade models shows that the steady-state fraction of covalently modified interconvertible enzyme is a function of 10 different cascade parameters. Because each parameter can be varied independently, or several can be varied simultaneously, by single or multiple allosteric interactions of ligands with one or more of the cascade enzymes, interconvertible enzymes are exquisitely designed for the rigorous control of key metabolic steps. Compared with other reglatory enzymes, they can respond to a greater number of allosteric stimuli, they exhibit greater flexibility in overall control patterns, and they can generate a greatly amplified response to primary allosteric interactions of effectors with the converter enzymes. Contrary to earlier views, the decomposition of ATP associated with cyclic coupling of the covalent modification and demodification reactions is not a futile process. ATP decomposition supplies the energy needed to maintain concentrations of modified enzyme at steady-state levels that are in excess of those obtainable at true thermodynamic equilibrium.


Concept of internal structural controls for evaluation of inactive synthetic peptide analogs: synthesis of [Orn13,14]apamin and its guanidination to an apamin derivative with full neurotoxic activity. The importance of arginine residues 13 and 14 in the bee venom neurotoxin, apamin, was teste by the synthesis of replacement analogs. [13,14-di-Ndelta-trifluoroacetylornithine]Apamin was synthesized by the solid phase method on a benzhydrylamine resin. It was deprotected to [13,14-diornithine]apamin, which was then guanidinated to produce the 4-homoarginine-13,14-diarginine analog, [Har4]apamin. Neither the trifluoroacetylornithine analog nor the ornithine analog produced any detectable symptoms when injected intravenously into mice. However, the synthetic [Har4]apamin exhibited the full neurotoxic activity of native apamin and of [Har4]apamin derived from the natural toxin. This provided an internal structural control for the correctness of the primary structure of the inactive synthetic analogs and strengthened the conclusion that one, or both, of the arginine residues plays an important role in the action of apamin.


Discontinuous replication of replicative form DNA from bacteriophage phiX174. Bacteriophage phiX174 DNA has been labeled with short pulses of [3H]thymidine during synthesis of replicative form molecules in infected Escherichia coli HF4704 cells. The replicating phiX174 DNA was isolated and analyzed by sedimentation in an alkaline sucrose gradient. During a brief pulse (5 sec at 30 degrees), the radioactivity incorporated into the complementary strand was found in chains much shorter than one genome length. Of the radioactivity incorporated into the viral strand, two-thirds was in the short pieces and the rest was in chains of one genome length or longer. RNA attachment to the 5' end of both strand components of the nascent short pieces was shown by the appearance of spleen exonuclease-digestable nascent molecules after alkali treatment. These observations suggest that the viral as well as the complementary strand is synthesized by the discontinuous mechanism with RNA primers during replication of duplex phiX174 DNA.


Nerve growth factor receptors: identification of distinct classes in plasma membranes and nuclei of embryonic dorsal root neurons. Two classes of receptors for 125I-labeled nerve growth factor in chick embryonic dorsal root neurons have been observed. One type is associated with the plasma membrane (or microsomal fraction) and can be completely solubilized by Triton X-100. These receptors display the nonsaturable binding isotherms and curvilinear Scatchard plots previously reported for nerve growth factor receptors in whole cells. The second class of binding sites is located in the nucleus, firmly bound to chromatin. These receptors are not solubilized by detergent, show saturable binding, and yield linear Scatchard plots of the type associated with a single class of binding sites of high affinity. The presence of the two receptor types suggests a bimodal mechanism of action for nerve growth factor.


Isolation and identification of aliphatic short-chain acylcarnitines from beef heart: possible role for carnitine in branched-chain amino acid metabolism. Aliphatic acylearnitines isolated from a water-soluble fraction of beef heart have been characterized by gas chromatography and mass spectrometry. The following acyl residues derived from the acylcarnitine fraction were unequivocally identified: acetyl, propionyl, isobutyryl, butyryl, alpha-methylbutyryl, valeryl, isovaleryl, tiglyl, and caproyl. beta-methylcrotonyl and methacrylyl were tentatively identified. This occurrence of considerable quantities of branched-chain acylcarnitines indicates a role for carnitine in branched-chain amino acid metabolism.


Molecular weight of bacteriorhodopsin solubilized in Triton X-100. Bacteriorhodopsin from Halobacterium halobium has been solubilized in the nonionic detergent Triton X-100. The circular dichroic spectrum and hydrodynamic properties indicate that the structure of this protein in the detergent is not significantly altered from that of the native membrane-bound form. Bacteriorhodopsin is monomeric under the conditions of solubilization with a molecular weight of 24,250+/-2,000 and binds approximately one micelle of Triton X-100.


Selective association of the trout-specific H6 protein with chromatin regions susceptible to DNase I and DNase II: possible location of HMG-T in the spacer region between core nucleosomes. Nuclei and chromatin from trout testis cells were digested with three different nucleases (DNase I, DNase II, and micrococcal nuclease), and the acid-soluble proteins that were solubilized and those remaining bound to the nuclease-resistant DNA were compared electrophoretically. With the conditions described by H. Weintraub and M Groudine [(1976) science, 193, 848-856], which we previously found to be selective in digesting actively transcribed regions in trout testis chromatin, a single chromosomal protein, H6, was solubilized. The nucleosomal histones and H1 remained insoluble, bound to the resistant DNA. In contrast, digestion with micrococcal nuclease led to a preferential solubilization of a second protein, HMG-T, together with the release of some nucleosomal histones and H1 into the soluble fraction. DNase II also discriminated between "active" and "inactive" chromatins; when a DNase II-solubilized "active" chromatin fraction was prepared, it too was enriched in H6 and HMG-T. Thus, both H6 and HMG-T, the two major low-salt extractable chromosomal nonhistone the two major low-salt extractable chromosomal nonhistone proteins from trout testis, are associated with chromatin regions selectively sensitive to nucleases. The preferential solubilization of HMG-T by micrococcal nuclease action suggests that it might be located at the internucleosomal "spacer" region.


DNA or RNA priming of bacteriophage G4 DNA synthesis by Escherichia coli dnaG protein. Escherichia coli dnaG protein is involved in the initiation of DNA synthesis dependent on G4 or ST-1 single-stranded phage DNAs [Bouche, J.-P., Zechel, K & Kornberg, A. (1975) J. Biol. Chem. 250, 5995-6001]. The reaction occurs by the following mechanism: dnaG protein binds to specific sites on the DNA in a reaction requiring E. coli DNA binding protein. An oligonucleotide is synthesized in a reaction involving dnaG protein, DNA binding protein, and DNA. With G4 DNA this reaction requires ADP, dTTP (or UTP), and dGTP (or GTP). Elongation of the oligonucleotide can be catalyzed by DNA polymerase II or III in combination with dnaZ protein and DNA elongation factors I and III, presumably by the mechanism previously reported [Wickner, S. (1976) Proc. Natl. Acad. Sci. USA 73, 3511-3515] or by DNA polymerase I.


Structural convergence during protein evolution. Several recent protein crystallographic structure determinations have demonstrated the existence of considerable tertiary structural similarity among proteins otherwise having little similarity in either amino acid sequence or biological function. In order to assess the possibility that such proteins may have arisen through processes of divergent evolution from a common ancestor, a graphical presentation is given which correlates the pattern of allowed single base substitutions defined by the genetic code with the associated changes in the structural properties of the encoded amino acids. The results show that while a large degree of structural conservation is evident due to codon synonomy, there is, in general, little tendency for the code to be structurally conservative in the majority of the cases where codon single-base changes result in amino acid substitutions. The possible consequences of this pattern of potential amino acid substitutions are discussed in relation to protein evolutionary processes.


Method for obtaining a high resolution protein map starting from a low resolution map. A method is described for estimating the phases of high resolution single-crystal diffraction data from proteins, by using as a starting point a set of low resolution phases (about 3 A) derived by multiple isomorphous replacement (or other) methods. The method consists in refining by least-squares the positions and thermal parameters of a set of dummy atoms placed in the initial low resolution electron density map, so as to minimize the discrepancy between the calculated scattering intensities and the scattering intensities observed in the high resolution data set. Phases calculated from these refined atomic positions are used to extend the resolution and to improve the quality of the electron density map. The success of the method depends on a new least-squares algorithm that has a radius of convergence of about 0.75 A. This large radius of convergence, together with the severe restrictions placed on the initial positions of the dummy atoms by the requirement that they lie within limited regions of the isomorphous electron density map, and the constraint imposed by the polymeric nature of a polypeptide chain account for the success of the method. The method has been successfully used to phase the structure factors of 2-zinc insulin at a resolution of 2 A and 1.5 A, starting from a set of isomorphous phases at 3-A resolution.


The living state and cancer.

The living state and cancer. Complex living structures developed on our globe after the appearance of light and oxygen. In functions of these structures, solid state phenomena play a major role. The structural proteins were made into radicals by doping, the covalent incorporation of electron acceptors. This lent mobility to their electrons and a subtle reactivity to their molecules. Cancer is unable to go into the radical state.


Extensive disulfide bonding at the mammalian cell surface. Cell surface proteins of cultured cells are disulfide bonded to a greater degree than are total cellular proteins. In particular, the "large external transformation-sensitive" (LETS) protein, a major surface protein, is present almost exclusively in disulfide-bonded complexes including homodimers and also higher aggregates held together by disulfide bonds or concovalent interactions. Other cell surface proteins also appear to be involved in disulfide bonding, both intramolecular and intermolecular. In virally transformed cells, LETS protein and its disulfide complexes are absent and certain other disulfide-bonded proteins are also not observed.


Effects of antitubulins on the redistribution of crosslinked receptors on the surface of fibroblasts and epithelial cells. Substrate-attached normal mouse fibroblasts, transformed mouse fibroblasts (L strain), and epithelial cells (MPTR strain) were incubated with two ligands crosslinking different groups of the surface receptors: concanavalin A and cationic ferritin. Surface-attached ligands were revealed by an indirect immunofluorescence method. Incubation of control cells with these ligands induced the patching of corresponding surface receptors and the clearing of these receptors from the surface zones located on the lamellar cytoplasm near cell edges actively protruding pseudopodia. Effects of three antitubulins (microtubule-destroying drugs: Colcemid, colchicine, and vinblastine) on the ligand-induced redistribution of receptors were investigated and compared with the previously described effects of these drugs on the distribution of active cell edges. Incubation of normal and transformed fibroblasts with these antitubulins led to the disappearance of nonactive cell edges; the whole cell perimeter became active. Correspondingly, the clearing pattern of the surface receptors of fibroblasts was altered by antitubulins: the cleared area in antitubulin-treated cells formed a circular band along the whole peripheral cell edge. In epithelial cultures, in contrast to fibroblastic ones, antitubulins changed neither the distribution of the active sites of the surface nor the distribution of the areas cleared of crosslinked receptors. Thus, the specific ability of the surface areas located near the active cell edges to become cleared of crosslinked receptors is characteristic not only for the cells with intact microtubules, but also for the cells with microtubules destroyed with antitubulins.


Regulation of DNA synthesis: age-dependent cooperation among G1 cells upon fusion. The object of this study was to determine whether the inducer(s) of DNA synthesis in mammalian cells accumulates gradually throughout the G1 period or becomes available suddenly at the G1-S transition. HeLa cells, synchronized at various points in the G1 period, were fused by using UV-inactivated Sendai virus. Early G1 cells were fused with mid-G1 or late G1 cells and late G1 cells were fused with mid-G1 cells. The G1 traverse of mono-, bi-, and trinucleated cells was studied. The bi- and trinucleated cells of mid-G1 and late G1 parents traversed the G1 period significantly faster than did their mononucleated counterparts. The reduction in the duration of the G1 period was proportional to the number and age of nuclei at the time of fusion. There was no significant difference between the mono- and binucleated cells of the early G1 parent in their rates of entry into S period. In light of these findings, a model is proposed in which the inducer(s) of DNA synthesis accumulates gradually throughout the G1 period, reaching a critical level at the G1-S boundary when DNA replication is initiated; after reaching a peak during early or mid-S period, it declines to below the critical level when DNA synthesis ceases.


Inhibition of cytokinesis in Friend leukemia cells by membrane mobility agents. Treatment of a line of Friend leukemia cells with a dispersion of the membrane mobility agent, A2C, yields cells that undergo successive nuclear divisions without cytokinesis, resulting eventually in cells with as many as 30 nuclei. Neither the DNA replication rate of the cells nor the generation time is different after treatment; in addition, the multiple nuclei divide synchronously, and the chromosome number corresponds to the number of nuclei in the cell. Inhibition of cytokinesis is not observed if the cells are washed with reagent-free medium within 1 hr of treatment, but is observed if washing is delayed for 24 hr. Membrane mobility agent loaded with the fluorescent probe, Flomol F20C, leads to fluorescent membrane; fluorescence disappears from the membrane after a change of medium within 1 hr, but not after a change of medium within 24 hr. Some stages in the overall development resemble those seen for cytochalasin B inhibition of cytokinesis, although the mechanisms may well be different for the inhibition promoted by membrane mobility agent. The inhibition of cytokinesis by A2C provides a potentially interesting means of studying cytokinesis and the regulation of differentiation.


Tumor promoters inhibit spontaneous differentiation of Friend erythroleukemia cells in culture. Clones of Friend erythroleukemia cells, characterized by the presence of 40-70% benzidine-positive cells synthesizing hemoglobin in the absence of inducing drugs, were treated with several phorbol diesters with a known range of tumor-promoting activity on mouse skin. Good correlation was found between the reported tumor-promoting activity of a particular phorbol diester and its ability to inhibit spontaneous erythroid differentiation in culture. The inhibition of differentiation by 12-O-tetradecanoyl-phorbol-13-acetate, the most active tumor promoter, was maximum after 4 days of treatment; this inhibition was reversed by removal of the phorbol diester no matter how long the period of treatment. Unlike control cells, which gradually revert to a population with a low percentage of benzidine-positive cells, cells treated with 12-O-tetradecanoyl-phorbol-13-acetate retained a high potential for spontaneous differentiation.


Independent expression of the adrenergic phenotype by neural crest cells in vitro. Neural crest cells obtained from Japanese quail and grown in vitro without other embryonic tissues differentiate into adrenergic cells. These cells show intense catecholamine-specific histochemical fluorescence, and some have long, varicose neuronal processes. Ultrastructural examination shows two populations of cells, one with small (about 90 nm) dense-core vesicles resembling principal sympathetic neurons and the other with larger (about 150 nm) dense-core granules resembling chromaffin or small intensely fluorescent cells. Neuronal cells without adrenergic characteristics are also present. These results are compatible with the hypothesis that a population of cells determined along neuronal lines exists in the neural crest prior to migration.


Food, drug, and cosmetic dyes: biological effects related to lipid solubility. Food, drug, and cosmetic dyes of the xanthane type (analogs of fluorescein) were applied to isolated molluscan ganglia and changes in the electrophysiological properties of identified neurons were monitored. The synthetic coloring agents increased the resting membrane potential and conductance of the neurons in a dose-dependent manner by increasing the potassium permeability of the membrane relative to that of other ions. The relative activity of these anionic dyes was highly correlated with their lipid solubility. The structure-activity study of the effects of the dyes on molluscan neurophysiology provides a basis for estimating the toxicity and brain uptake of the dyes in vertebrates, and predicting their effects on metabolism and blood clotting.


Hemoglobin F synthesis in vitro: evidence for control at the level of primitive erythroid stem cells. The in vitro regulation of fetal hemoglobin (HbF was investigated in clones of cultured adult human erythroid cells by in situ immunofluorescent identification of the hemoglobins synthesized. Formation of Hb F-containing clones was enhanced by erythropoietin and by culture conditions favoring the proliferation of less-differentiated stem cells of the burst-forming-unit type. Burst-forming units differed in their capacity to direct Hb F synthesis in their terminally differentiated progeny. A class of early precursors that can produce descendent stem cells with or without commitment to Hb F production was identified. The findings suggest that the capability for expression of Hb F in terminally differentiated cells of the adult is determined at the level of less-differentiated erythroid stem cells with characteristics of burst-forming units. It is proposed that the regulation of Hb F synthesis in vivo is also linked to the process of differentiation of the erythroid stem cells and that the patterns of Hb F synthesis during ontogeny reflect the attainment of progressively higher levels of differentiation of erythroid stem cells as development proceeds.


Epigenetic variation of cultured somatic cells: evidence for gradual changes in the requirement for factors promoting cell division. Cells of higher plant species in culture sometimes lose their requirement for an exogenous supply of a cell division factor that, thereafter, they are able to produce. This heritable change, known as cytokinin habituation, appears to be an epigenetic one rather than a classical mutation because it is directed, potentially reversible, leaves the cell totipotent, and involves the expression of a latent differentiated function. By using cloned cell lines derived from pith parenchyma of tobacco, we have obtained evidence that the habituation process is gradual rather than all-or-none and leads to progressively more autotrophic tissues. Cells in culture show reversible shifts among a range of habituated states but remain totipotent and can be induced to regain their requirement for a cell division factor. Thus, it appears that habituation involves epigenetic changes in a quantitative cellular phenotype. Our findings support the hypothesis that tumor progression in crown gall, a neoplastic disease of higher plants, can be accounted for by heritable changes in the pattern of gene expression.


Serial transfer of a human gene to rodent cells by sequential chromosome-mediated gene transfer. The human hypoxanthine phosphoribosyl-transferase (IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) gene (hprt) has been serially transferred to mouse cells and then to Chinese hamster fibroblasts by two cycles of metaphase chromosome isolation and incubation with recipient cells. Human metaphase chromosomes were incubated with mouse A9 cells deficient in hypoxanthine phosphoribosyltransferase, and independent colonies expressing the human species form of this gene were isolated in a selective medium. Metaphase chromosomes isolated from two of these clonal lines were incubated with Chinese hamster fibroblasts deficient in hypoxanthine phosphoribosyltransferase; five resulting independent colonies again expressed the human species of this gene. The transfer frequencies in the two cycles of chromosome-mediated gene transfer were similar (about 10(-7)). These results indicate that the transferred human chromosome fragment is closely associated with the chromosomes of the mouse A9 cells and it is probably integrated into the chromosomal DNA of the recipient cell.


Detection of active heteropolymeric beta-glucuronidase in hybrids between mouse cells and human fibroblasts with beta-glucuronidase deficiency. Heteropolymeric beta-glucuronidases are detected in somatic cell hybrids between mouse cells and human fibroblasts deficient in beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase, EC 3.2.1.31) by electrophoresis and column chromatography. Specific antisera against human beta-glucuronidase prepared in mice recognize these heteropolymeric beta-glucuronidases. Our results demonstrate that synthesis of mutant subunits of variant beta-glucuronidase continues in deficient human fibroblasts; these mutant subunits of human beta-glucuronidase retain the ability to associate with normal subunits of mouse beta-glucuronidase to form the enzymatically and immunologically active tetramer. These studies demonstrate the usefulness of interspecific cell hybrids for study of structural gene mutations of polymeric enzymes, such as those of beta-glucuronidase in mucopolysaccharidosis type VII.


Production of antibodies against influenza virus by somatic cell hybrids between mouse myeloma and primed spleen cells. We have produced somatic cell hybrids between mouse myeloma cells and spleen cells derived from a BALB/c mouse immunized with purified influenza virus. The hybrid cells were found to produce large amounts of antibodies specific for the hemagglutinin of the virus and were able to induce tumor formation when injected into BALB/c mice.


Glycolipid-bound sialic acid in serum: increased levels in mice and humans bearing mammary carcinomas. In mice bearing transplantable mammary carcinomas, serum levels of sialic acid-containing glycolipids were elevated 2.5-fold in pooled serum samples from which gangliosides were purified by column chromatography. A method is also described by which ganglioside content was estimated on as little as 1.0 ml of whole blood to permit studies with individual tumor-bearing mice and age- and litter-matched controls. Using this method, we observed similar elevations in ganglioside levels that were independent of age and sex of the animal and appeared in advance of palpable tumors. Following excision of the tumors, the glycolipid sialic acid values dropped below control levels and remained there. Serum sialic acid of the glycolipid fraction was elevated nearly 2-fold in human carcinoma patients and appeared to decline after surgery.


Isoantigenic expression of Forssman glycolipid in human gastric and colonic mucosa: its possible identity with "A-like antigen" in human cancer. The heterogenetic Forssman antigen is a glycosphingolipid, a ceramide pentasaccharide with the structure GalNAcalpha1-->3GalNAcbeta1-->3Galalpha1-->4Galbeta1-->4Glc-->ceramide. Forssman-positive animals are capable of synthesizing this compound in tissues or in erythrocytes, in contrast to the Forssman-negative species, including humans, which are incapable of adding the last carbohydrate in the sequence of the Forssman antigen, namely alphaGalNAc. The Forssman glycolipid and its precursor globoside were examined in twenty-one samples of surgically extirpated gastrointestinal mucosa and tumors derived therefrom. The results revealed that a few patients had chemically and immunologically detectable levels of the Forssman glycolipid as a normal component of their gastrointestinal mucosa (F(+) population); in contrast, the majority of patients did not contain this glycolipid in their normal mucosa (F(-) population). Whereas the F(-) population included blood groups A, B, and O, the F(+) population did not correspond to blood group A. The Forssman status in tumors taken from the F(+) or F(-) population showed the following striking features: (i) all tumors derived from F(-) mucosa possessed Forssman glycolipid, whereas (ii) none of the tumors originating in F(+) mucosa contained Forssman glycolipid. Globoside, the immediate precursor of Forssman antigen, was distributed equally among F(+) and F(-) mucosa and the tumors derived therefrom. Thus, the expression of Forssman antigen in gastrointestinal mucosa appears akin to that of an isoantigen. Furthermore, the Forssman antigen that appears in tumors of the F(-) population could represent a human tumor-associated antigen. In view of the strong crossreactivity of Forssman antigen with blood group A determinants, the appearance of Forssman antigen in human tumors could be related to the "A-like antigen" (or "neo-A antigen") of human tumors reported previously [Hakomori, S., Koscielak, J., Black, K. J. & Jeanloz, R. W. (1967) J. Immunol. 98, 31-38; Häkkinen, I. (1970) J. Natl. Cancer Inst. 44, 1183-1193].


Cholecystokinin and its COOH-terminal octapeptide in the pig brain. Two components--one resembling intact cholecystokinin in size and charge and immunologic specificity, and the other resembling the COOH-terminal octapeptide of cholecystokinin--have been found in extracts of the pig cerebral cortex. The relative concentrations of the two peptides in the extracts were dependent on the extractant, boiling 0.1 M HCl being more effective than boiling water for the extraction of intact cholecystokinin but less effective for the extraction of the octapeptide. The physiologic role of these peptides in the brain has yet to be elucidated.


In vitro and in vivo correlation of clotting protease activity: effect of heparin. The thrombogenicity of three highly purified proteases (thrombin, activated Factor X, and activated Factor IX) was determined quantitatively in an animal model. The minimal amounts required to produce a standard score 4 thrombus were 1.1 nmol for thrombin, 0.12 nmol for activated Factor X, and 0.018 nmol for activated Factor IX. After the administration of heparin at 5, 10, and 20 units/kg in rabbits, the thrombogenicity of each of these proteases decreased progressively. The heparin-induced inhibition of thrombosis decreased in the order, activated Factor IX > activated Factor X > thrombin at each heparin concentration. These differences were statistically significant. These in vivo data provide support for the following hypotheses originally developed from in vitro experiments: (i) activation of the blood coagulation system, which proceeds through a cascade mechanism, incorporates biochemical amplification; (ii) the inhibition of activated Factor IX by antithrombin III in the presence of heparin is an important reaction in the prevention of thrombosis; (iii) less heparin is required to inhibit thrombosis prior to thrombin generation than afterward; (iv) an increase in the reactivity of antithrombin III reflects a decreased tendency to thrombosis while a decrease in this reactivity reflects an increased tendency to thrombosis.


Fatty liver induced in Zucker "fatty" (ff) rats by a semisynthetic diet rich in sucrose. A new fatty liver model is described in which heredity plays a major role. A marked fatty liver develops when the homozygous mutant Zucker rat (ff or "fatty") is fed a semisynthetic diet enriched in sucrose. Lean littermates do not develop fatty liver on this experimental diet. Even old ff rats do not develop fatty livers on chow; the experimental diet is required. The fatty liver is described, including light microscopic and preliminary electron microscopic observations.


Measurement of daily cholesterol synthesis rates in man by assay of the fractional conversion of mevalonic acid to cholesterol. A significant correlation has been found in man between total daily cholesterol synthesis rates as determined by sterol balance measurements and the fraction of intravenously administered R-[5-14C]mevalonic acid converted to cholesterol. In 30 studies it was found that the mean daily cholesterol synthesis rates estimated by sterol balance measurements ranged from 395 to 3047 mg/day, whereas the fractional conversion of mevalonate to cholesterol varied from 0.28 to 0.99. The two parameters correlated with a coefficient of 0.87, P less than 0.001. This method for estimating cholesterol synthesis rates requires low doses of radioisotopic materials (25 muCi of [14C]mevalonate and 5 muCi of [3H]cholesterol) and less than 1 hr of the patient's time; it can be repeated at intervals of 3 weeks and reflects cholesterol synthesis over a short period of time.


Authentic beta-globin mRNA sequences in homozygous betaO-thalassemia. In a patient with homozygous betaO-thalassemia in whom studies of reticulocyte hemoglobin synthesis showed no beta-globin chain synthesis in vivo and in vitro, molecular hybridization studies revealed RNA sequences complementary to beta-globin cDNA. The fact that these sequences were authentic beta-globin mRNA was shown by fingerprint analysis of T1 ribonuclease-digested mRNA and by sequencing of oligonucleotides unique to beta-globin mRNA. The beta-mRNA that failed to direct beta-globin chain synthesis was not detectably shortened or degraded and contained poly(A) sequences.


Variation in ability of measles virus plaque progeny to induce interferon. Plaque progeny of three interferon (IF)-inducing strains of measles virus (Edmonston, Schwarz, and CC) were examined for ability to induce IF in BSC-1 cells. Only after passage in Vero cells did any of the Edmonston progeny induce IF. The vast majority of plaque progeny selected from the Schwarz strain induced IF, even though this virus was originally derived from the Edmonston strain. This property was retained even after serial plaque purification of the progeny. However, the Schwarz-derived CC strain consisted of a population generally unable to induce IF. Stocks grown from both Edmonston and CC plaques demonstrating the IF+ phenotype maintained this characteristic as a whole, but it was not a property that was inherited by all progeny in the stocks. Levels of IF induced were approximately the same for all strains, even though the proportion of inducing progeny varied markedly among them. These noninducing variants appeared to be normal, fully infectious measles virions. The results suggest that induction of IF by measles virus is at least partially under the genetic control of the virus.


Nonlinear analysis of cat retinal ganglion cells in the frequency domain. We have analyzed the responses of cat retinal ganglion cells to luminosity gratings that are modulated in time by a sum of sinusoids. A judicious choice of the component temporal frequencies permits a separation of the linear and second-order nonlinear components. Y cell responses show harmonic generation and intermodulation distortion over a wide frequency range. These nonlinear components predominate over the linear components for certain types of spatial stimuli. Nonlinear components in X cells are greatly diminished in comparison. The character of the nonlinear responses provides strong constraints on prospective models for the nonlinear pathway of the Y cell.


Modulation of acetylcholine receptor by antibody against the receptor. Antibody against acetylcholine receptor induces an increase in the rate of degradation of acetylcholine receptors on a mouse cell line (BC(3)H-1) and cultured rat skeletal muscle. The increased rate of degradation results in a lowered density of acetylcholine receptors on muscle membrane and a lowered sensitivity to iontophoretically applied acetylcholine. The modulation of acetylcholine receptor is energy, temperature, and time dependent and may be related to antigenic modulation found in other systems. Acetylcholine noise analysis demonstrates that antibody against acetylcholine receptor reduces the channel mean conductance and mean open time slightly. It is concluded that antibody binds to the acetylcholine receptor, impairs its function, and induces receptor degradation. This results in a lowered density of acetylcholine receptor and a lowered sensitivity to acetylcholine. Patients with myasthenia gravis have antibodies to their acetylcholine receptor in their serum. Antigenic modulation of receptor in the muscle of patients with myasthenia gravis could contribute to the observed decrease in amplitudes of miniature endplate potentials and in muscle acetylcholine sensitivity, and the symptoms of muscular weakness.


Lithium efflux through the Na/K pump in human erythrocytes. ACTIVE LI EFFLUX FROM HUMAN ERYTHROCYTES WAS SHOWN TO BE MEDIATED BY THE NA/K PUMP: (i) intracellular Li (Li(c)) activated ouabain-sensitive K influx, and (ii) a portion of the Li efflux required external K and was inhibited by ouabain. In activating K influx, Li(c) interacts with the pump like Na rather than like K-depleting the cells of orthophosphate inhibited activation of K influx by intracellular K (K/K exchange) but did not inhibit Li-activated K influx. (To show these interactions of Li(c) with the Na/K pump, p-chloromercuribenzenesulfonate or nystatin was used to allow replacement of intracellular Na and K with Li and choline.) From kinetic studies of the pump, it was shown that the apparent affinity of the intracellular aspect of the Na/K pump for Li was an order of magnitude less than that for Na. From simultaneous measurements of ouabain-sensitive net fluxes of Li and K in Na-free cells, it was shown that the pump-mediated K influx and Li efflux were coupled. The stoichiometry of the coupling ratio was close to 1:1 for Li:K, different from the coupling ratio of 3:2 for Na:K in the pump's normal mode of operation. It had been shown previously that the Na/K pump in human erythrocytes mediates active Li influx. Because it also mediates active Li efflux, the molecular mechanisms for distinguishing between Na and K must be qualitatively different at the internal and external aspects of the pump. The possible relevance of the results of this study to manic depressive illness and Li therapy is discussed.


N5-Methyltetrahydrofolate-homocysteine cobalamin methyltransferase activity in chronic erythremic myelosis (Di Guglielmo syndrome).


A simple ventilator suitable for neurophysiologic studies of small animals.


Hyperthermic treatment of tumours: experimental and clinical applications.


An epidemiological and evolutionary approach to the recombinant DNA problem.


Swimmer's itch--a Rhode Island malady.

Swimmer's itch--a Rhode Island malady.


A home program for improving voice and speech quality of infants with repaired cleft palate.


An analysis of controlled substances Rx forgeries in Rhode Island.


Bacteria in cavities beneath intermediary base materials. The ability of six different intermediary base materials to prevent bacterial entrance beneath silicate cement fillings was investigated in vivo in primary molars. After an observation period of 1 month, bacteria were found on the pulpal wall in two out of 10 cavities beneath Fluoritec and four out of 10 cavities beneath Durelon solid mixed, De Trey phosphate cement solid or creamy mixed. Beneath the intermediary base materials Dycal, zinc oxide-eugenol cement, Dropsin and Durelon creamy mixed, no bacteria were found. In cavities filled with silicate cement or silver amalgam only, bacteria were observed in nine out of 10 and in five out of 10 cavities, respectively.


Binding of dyes to chlorhexidine-treated hydroxyapatite. The binding of some selected food dyes to hydroxyapatite with and without a coating of chlorhexidine was studied. The apatite had bound 0.6 mumol chlorhexidine per g dry weight. The bound chlorhexidine was in equilibrium with a free concentration of 115 microgram ml (128 micron). The dyes investigated were brilliant blue (FD&C Blue No. 1), indigo carmine (FD&C Blue No. 2), tartrazine (FD&C Yellow No. 5), sunset yellow (FD&C Yellow No. 6), amaranth (FD&C Red No. 2), and riboflavin. Riboflavin did not bind to either chlorhexidine-treated apatite or untreated apatite, whereas the other dyes showed a considerable affinity for chlorhexidine-treated apatite as compared with untreated apatite. Because the dyes with binding ability possess two or three acidic groups, and because riboflavin has none, it was suggested that the binding of the dyes is mediated by an interaction between the anionic groups of the dye molecules and the cationic groups of the chlorhexidine molecules. The results are discussed and related to the formation of the brownish discolorations seen on the teeth of patients using chlorhexidine mouthrinses. A mechanism to explain the development of tooth stains is proposed.


Lipidhistochemical and microradiographic study of distribution of lipids in relation to mineral content in dentin caries. Fifteen human molars were investigated using lipidhistochemical and microradiographic methods. A peripheral necrotic and totally decalcified part of the carious lesion revealed a markedly positive staining reaction for sphingomyelin, sulfatides, cholesterol- and/or triglyceride-esters. The reaction was probably conditioned by the presence of debris and plaque within this area. Pulpally and immediately below the necrotic zone, an area of demineralization was found which on the microradiographs appeared as a radiolucent zone. The zone showed a mineral gradient with an increasing mineral content towards the pulp. In the zone of demineralization a positive reaction occurred for sphingomyelin decreasing in a pulpal direction with increasing mineral content. A weakly positive reaction for cholesterol- and/or triglyceride-esters was also detected but only in the most pulpal part of the zone of demineralization; the intensity of the staining reaction was comparable to that found in normal dentin. In those areas which were represented by a sclerotized, radiopaque zone, only a very weak reaction for sphingomyelin, cholesterol-and/or triglyceride-esters could be observed of the same staining intensity as in normal dentin. The region between the lesion and the pulp showed the same staining intensity as normal dentin.


A longitudinal study on the effect of unilateral extraction of primary molars. The effect of unilateral extraction of the first or second primary molar on space conditions, need for orthodontic treatment, and eruption stage of permanent canines and second molars has been studied longitudinally in two groups. In Group 1 the first primary molar had been extracted early in 13 cases in the maxilla and in 14 cases in the mandible. In Group 2 the corresponding figures for the second primary molar were 14 and 24 for the maxilla and mandible, respectively. The space on the extraction side in Group 1 was significantly less than on the control side at the age of 9 but not at the age of 13. In Group 2 there was significantly less space on the extraction side than on the control side at the two registration ages (10.5 and 12 years). Need for orthodontic treatment was low in Group 1 and high in Group 2. As for eruption stage of permanent canines and second molars, no significant differences were found between the extraction side and the control side in the two groups.


Quantitative observation on teeth during calcium deprivation in rats. Adult female rats were subjected to severe calcium deprivation by feeding them a calcium-deficient diet containing oxalate (Group A). Furthermore, pregnant and lactating animals were subjected to the same diet (Group B). The mandibular teeth were collected for ash determination and for linear measurements. The ash content of the growing incisors was only slightly reduced in Group A, while the reduction in Group B was 27%. Linear measurements demonstrated that the outer dimensions of the incisors were not affected by the calcium-depriving regimen in either group, while the inner dimensions (pulp cavity) were considerably increased in Group B due to reduced thickness of the dentin mantle. The daily dentin apposition in Group A did not deviate much from the control values, while in Group B it was severely reduced. The thickness of incisor enamel was unaffected by the calcium-depriving regimen. The ash content of the molars was normal in Group A, but slightly reduced in Group B.


Enzymatic iodination of salivary proteins by the 125I-lactoperoxidase system. Purified milk lactoperoxidase and endogenous human salivary peroxidase were used to label the proteins of whole mouth saliva with [125I]iodide. The proteins were then analyzed by isoelectric focusing or they were subjected to one-dimensional polyacrylamide gel electrophoresis at pH 8.4. The radioactivity of the resolved protein fractions was determined. There were three to four major and four to five minor areas of radioactivity which were carried together with more or less distinctive protein fractions. Amylase and albumin were shown to be the most effective in binding [125I]iodide. No significant differences were observed in the iodination patterns of salivary proteins iodinated in the presence of endogenous saliva peroxidase and those iodinated in the presence of added milk lactoperoxidase. Hydrogen peroxide was necessary for iodination to take place. The significance of iodoproteins and the role of salivary peroxidases in the nonthyroidal metabolism of iodine are discussed.


On human amylase isoenzymes.

On human amylase isoenzymes.


Genetic engineering.

Genetic engineering.


Treatment of confusion.

Treatment of confusion.


Seventy-five year old caucasian male with jaundice and back pain.


Clinicopathological conference: Sixty-five year old caucasian male with fever and chest pain for 8-10 days.


Graduate medical education in South Dakota.


A matrix system for class II amalgam restorations in primary molars.


Masseter motor pause frequency in full denture wearers as related to different food textures.


Stability of rapid dental radiographic developing solutions.


Light cross orientation for lateral cephalograms.


Postural position of the mandible with ear-plug fixation and light-cross orientation.


Dental caries and restorations in teenagers. I. Index and score system for radiographic studies of proximal surfaces. An index and a score system for radiographical longitudinal studies of caries progression on proximal tooth surfaces are presented and compared with the DF-surface system. Generally, a good correlation between DF-surface differences and scores was found in a three-year study on teenagers. However, the score system seems to forward better means for a detailed study of the individual.


Dental caries and restorations in teenargers. II. A longitudinal radiographic study of the caries increment of proximal surfaces among urban teenagers in Sweden. Within a group of 16 year old school children leaving the regular school dental care, the number of carious lesions and fillings in proximal tooth surfaces was radiographically studied, using an index system. Three years later, the same individuals were re-examined. The results showed that intact surfaces and surfaces with small carious lesions were more resistant to change than others. A minority of the individuals was found to be responsible for a majority of the lesions established during the three year interval. Generally, the progress of caries was slow.


Fluoride uptake and release in deciduous enamel after application of fluoride varnishes. An in vitro polit study.


Masseter motor pause frequency as related to different bolus sizes. The frequency of motor pauses in the masseter EMG is recorded for different bolus sizes of chewing gum on ten dentate subjects. The bolus sizes were from one two five tables of chewing gum, and the instructions to the subjects were to chew normally. No correlation between bolus size and frequency of motor pauses was found.


Specific conditions of distress in the dental situation. The general feeling of distress in the dental situation has been studied in 60 female dental patients and correlated to the following variables: Experimentally evaluated sensitivity to pain, self-rating and the dentist's rating of sensitivity to pain, the pain-threshold value in the teeth, the need of local anesthesia, extraversion-introversion, neuroticism, and some percept-genetic psychological measures of adaptive behavior. The subjects have also answered a questionnaire for grading their distress in regard to different aspects of the treatment-situation, which were combined into eight groups using factor analysis and then correlated to the general distress. The variables having a significant relation to distress in the dental situation were: the dentist's rating of the patient's sensitivity, the need of anesthesia, four groups of treatment-components and two of the percept-genetic measures. There was also a certain relation to the pain threshold in the teeth.


Dental caries and restorations in teenagers. III. Social factors and attitudes in relation to dental status and caries increment among urban teenagers in Sweden.


Traumatized primary incisors - follow-up program based on frequency of periapical osteitis related to tooth color.


Simple hysterectomy is inadequate therapy for invasive cervical cancer.


The diagnostic usefulness of electron microscopy investigation of orbital embryonal rhabdomyosarcomas. The ultrastructural study of three malignant orbital tumors, only one of which was correctly diagnosed as embryonal rhabdomyosarcoma upon histologic examination, is reported. In all 3 cases electron microscopic investigation revealed the presence of rhabdomyoblasts. These are easily recognizable in one case in which the diagnosis was made on the basis of the optical microscopic study. The other two cases needed further tests to evince rhabdomyoblasts. The importance of an ultrastructural study for a histogenetic characterization of this kind of tumor is emphasized. As far as embryonal rhabdomyosarcomas are concerned the electron microscopic study is possible, and it gives useful results even when material fixed with routine histologic methods (formalin, Bouin's solution) are used.


Merits of a pediatric specialty--one opinion.


Testicular torsion in neonates.

Testicular torsion in neonates.


Medical Grand Rounds from the West Virginia University Hospital. Pericarditis.


Traumatic fibromyositis: a critical review of an enigmatic concept. Traumatic fibromyositis is not an inflammation; there is no fever, leukocytosis or increased sedimentation rate; electrical characteristics and serum enzyme levels are within normal limits, and there are no observable pathologic alterations, although they have been carefully searched for. Recent attempts to express the effects of muscular sprain or strain as a biochemical disturbance expressed in an unusual pattern of lactate dehydrogenase isoenzymes appear not only to be technically flawed but inconsistent with results of conventional enzyme studies on other muscle and interstitial inflammations. In the author's view, "traumatic" fibromyositis is no more than a verbal construct arrived at by adding an adjectival modifier to the old terms for idiopathic rheumatic disorders. An examination of the evolution of the concept of traumatic fibromyositis shows that it lacks validity as a clinical diagnosis and ought to be abandoned.


Intraperitoneal drain in cholelithiasis operations. 571 patients were operated on for cholelithiasis, 70 acute cases and 501 chronic ones. On 142 cases of the latter type choledochus exploration was performed, while on the others only simple cholecystectomy was carried out. Intraperitoneal drain in the form of a latex tube was used on all the acute cases except 4, on all who underwent choledochus exploration except 3, and on 254 of the 359 chronic cases on whom simple cholecystectomy was performed. The analysi of the material shows that the indications for intraperitoneal drainage are not very convincing after cholecystectomy at a chronic stage, considering the amount of fluid drawn via the intraperitoneal drain and the complications that arose. After choledochus exploration, however, intraperitoneal drain serves its purpose in connection with the removal of the choledochus drain. Intraperitoneal drain should therefore be used when choledochus has been explored. In routine cases it should not be removed until the choledochus drain has been withdrawn.


Recent views on the control of anterior pituitary function.


Pre-ovulatory plasma levels of 17beta-oestradiol (E2) and conception in patients treated with gonadotrophins. Twenty-six patients seeking advice for sterility were given courses of treatment with HMG-HCG. Ovarian maturation was followed by daily evaluation of plasma 17beta-oestradiol concentrations. HCG was administered as soon as 17beta-oestradiol levels reached 250 pg/ml. In a first group of 7 amenorrheic patients with lack of oestrogen activity, a pregnancy rate of 71.4% and an ovulation rate of 91.7% were achieved. In a second group of 5 amenorrheic patients showing evidence of oestrogen activity, a pregnancy rate of 80.0% and an ovulation rate of 100% were obtained. In a third group of 14 oligomenorrheic patients, the pregnancy rate attained 71.4% and the ovulation rate 96.9%. The overall pregnancy rate was 73.0%. With this procedure of monitoring HMG-HCG treatment by means of plasma 17beta-oestradiol levels, the multiple pregnancy rate reached only 11.7% and only one case of mild ovarian hyperstimulation was observed. Pre-ovulatory and pre-conceptional 17beta-oestradiol concentration were identical with those observed in spontaneous ovulatory cycles with or without conception.


Biochemical substrate of androgenic actions at a cellular level in prostate, bulbocavernosus/levator ani and in skeletal muscle.


Conception, contraception and misconception. Because of Dr. G. A. Overbeek's interest and contributions in the field of oral contraception a survey is given of present leads and developments in this area. It is concluded that contraceptive preparations known under names such as: once-a-month pill, morning-after pill and post-coitum pill, although desired, do not really exist at the moment. It is further expected that oral contraception based on the inhibition of ovulation will stay with us for many years to come. Better preparations, not exclusively containing oestrogen progestagen combinations but possibly including a non-hormonal pituitary inhibitor as well, might be developed. This will allow better control over the endometrium, and the unwanted effects of the presently used hormonal substances. It is likely that an implantation-inhibiting compound or an abortifacient which acts shortly after implantation will be found. With respect to oral contraception for males it is concluded that, although inhibition of spermatogenesis with drugs is possible, a satisfactory contraceptive treatment for men is not yet available.


The influence of psychotropic drugs on the local cerebral glucose-utilisation of the rat.


Ion activities in reversible ischemia of the cat brain.


Cerebral function and energy metabolism at critical thresholds of oxygen availability: a study in rats during status epilepticus induced by bicuculline.


Oligemic-hypotension-induced changes in EEG,CBF and pO2 and their pharmacological modifications.


Two distinct types of inhomogeneous metabolic failure in cerebral oligemia.


Abnormalities associated with reversible and irreversible brain damage following a time varied oligemic insult.


Abnormalities of brain flow and metabolism during recovery from diffuse cerebral ischemia: dependence upon duration of ischemia.


Regional brain glucose metabolism during recovery from transient cerebral ischemia.


Delayed inhibition of protein synthesis during recirculation after compression ischemia of the rat brain.


Serial changes in cerebral blood flow and metabolism following cerebral anoxia in man.


Brain edema and angiographical hyperemia in postrecanalized cerebral infarction.


Hyperemia and brain swelling after recanalized cerebral infarction. Superficial and deep cerebral microvasculature changes after temporary occlusion of a middle cerebral artery in cats.


The effect of dextran on cerebral function and blood flow after cardiac arrest. An experimental study on the dog.


Effects of phenobarbital anaesthesia on postischemic cerebral blood flow and oxygen consumption in the rat.