Surveys of hospital infection in the Birmingham region. I. Effect of age, sex, length of stay and antibiotic use on nasal carriage of tetracycline-resistant Staphyloccus aureus and on post-operative wound infection. Cross-sectional surveys of infection in relation to ward structure and practice were made in 38 hospitals between 1967 and 1973, including repeat surveys in 12 hospitals. The survey team (a research nurse and a senior microbiologist or technician) visited one ward a day and entered data on patients, including appearance of wounds seen at change of dressings, on the structure of the ward, and on ward practices; bacteriological swabs were taken from noses of all patients and staff of wards visited and from infected or open wounds, also from some environmental sites. Effect of age, sex, length of hospital stay and antibiotic use on carriage of tetracycline-resistant Staphylococcus aureus and on post-operative sepsis are considered here.Clinical infection (sepsis), further classified as ;severe', ;moderate' or ;mild' in accordance with a code of physical signs, including inflammation and suppuration, was found in 6.1% of clean undrained operation wounds. Drained wounds and those through hollow, heavily colonized viscera (;contaminated' wounds) had higher sepsis rates than undrained and ;clean' wounds; there was less sepsis with closed drainage and with small drains. Staph. aureus (24%) was the commonest single bacterial species, but gram-negative bacilli (50%) were found in a much larger proportion of septic wounds. The results showed that the infection rate was lowest among patients between 20 and 40 years old. Infection was significantly more common in male than in female patients.Nasal carriage of tetracycline-resistant Staph. aureus, used as an index of hospital-acquired infection, was commonest in geriatric patients and least common in gynaecological patients. There was correlation between nasal carriage of tetracycline-resistant staphylococci and age of the patient, length of hospital stay, sex, (male greater than female), operative treatment, and treatment with tetracycline, ampicillin and nitrofurantoin, but not with penicillin.


An alternative to the anterior single-tooth removable partial denture.


Acid etch characteristics of prismless enamel.


Dental electroanalgesia: reversibility of impedance changes seen following application of direct current to dentin.


The immediate overlay denture.

The immediate overlay denture.


The subperiosteal implant denture--a case follow-up.


KDA sponsored term life insurance.

KDA sponsored term life insurance.


A pound of cure?

A pound of cure?


From the desk of the President.

From the desk of the President.


Guest editorial.

Guest editorial.


Conference on inflammation. Discussion.

Conference on inflammation. Discussion.


Role of immune complexes in human periapical periodontitis.


Radiographic interpretation of experimentally produced osseous lesions of the human mandible.


Endodontic complications in an irradiated patient.


Dental pain of galvanic origin: report of case.


The problems of publication.

The problems of publication.


Cardiac dysrhythmias during outpatient general anesthesia--a comparison study. Seventy-seven ASA Class I patients were studied to compare the cardiac dysrhythmias occurring during outpatient office general anesthesia for oral surgery to dysrhythmias occurring during outpatient medical and surgical office procedures without general anesthesia and to dysrhythmias occurring in inpatients having minor operating room procedures under general anesthesia. Eighty-eight percent of the operating room group, 81% of the oral surgery group, and 45% of the non-general-anesthetic group had some form of dysrhythmia. There was a statistically significant difference between the numbers of dysrhythmias that occurred in the general anesthetic groups and the non-general-anesthetic group. None of the dysrhythmias documented was of the potentially fatal or extremely serious category.


Carotid body tumors.

Carotid body tumors.


"Malignant schwannoma of the lingual nerve". A case report.


Tongue pressures and tooth stability after anterior maxillary osteotomy. Tongue pressures against the maxillary dentition during swallowing were measured in a series of ten patients who underwent anterior maxillary osteotomy for correction of protrusion. In these patients, tongue pressures were low initially, especially pressures by the sides of the tongue in the molar region. After surgical retraction of the incisors, tongue pressures increased, but the increases brought pressures up to normal levels from the previous abnormally low values. The data are consistent with the view that function (swallowing) adapts to oral form, rather than the other way around.


Studies on oral submucous fibrosis. IV. Connective tissue changes.


Compression osteosynthesis.

Compression osteosynthesis. Nearly all types of mandibular fractures have been treated successfully by compression osteosynthesis. Special instruments are required, the bone must be treated correctly, the fragments must be reduced exactly, and the plate must be adapted exactly. Basically, only lag screws are used when there is a lamellar fracture and when a large surface permits support; the dynamic compression plate with oblique lateral screw holes is indicated when the fracture runs transversely. The dynamic compression plate with oblique lateral holes and the additional inlay portion is indicated in oblique fractures and when the alveolar process is weak.


Clinicopathological conference. Case 20, part 1.


Surgical treatment of chronic osteomyelitis of the mandible resistant to intraarterial infusion of antibiotics: report of case. A 47-year-old man with chronic osteomyelitis of the mandible is described. The patient had frequent episodes of acute and subacute exacerbation at varying intervals for a period of six years in spite of extended antibiotic therapy. Intraarterial infusion of antibiotics through the superficial temporal artery also failed to cause any improvement. He was finally treated successfully by surgical intervention.


Carotid-cavernous sinus fistula after trauma to the head. The similarities between the various conditions described are remarkable. The orbital or frontal bruit and pulsating exophthalmos are common only to the carotid-cavernous fistula. A recent history of dental treatment, of facial infection with an elevated white blood cell count, and leukocytosis suggests cavernous sinus thrombosis. The superior orbital fissure syndrome and orbital apex syndrome occur most frequently in conjuction with Le Fort II and III fractures, which can involve the optic foramen and superior orbital fissure, therefore disrupting the sensory and motor innervation to the orbit and adjacent structures (Fig 4). Direct orbital trauma without evidence of fracture and with all symptoms mentioned, except infection, bruit, and pulsating exophthalmos, suggests orbital hematoma. A thorough differential diagnosis with complete data is essential for a correct diagnosis, thereby reducing morbidity by institution of the appropriate treatment. Treatments for carotid cavernous fistula have varied over the years--all aiming toward abolition of the fistula. Currently, the preferred treatment is the supraclinoid clamping of the internal carotid artery, followed by muscle embolization of the internal carotid artery distal to the bifurcation, and clamping of the internal carotid artery in the neck.


Local intractable jaw pain in Wallenberg syndrome.


Plasmacytosis of the gingiva.

Plasmacytosis of the gingiva.


Lymphangioma of the tongue: medical and surgical therapy. Therapy for lingual lymphangioma consists of the following: --medical therapy for acute swelling in the form of steroids, enzymes, and antibiotics; --surgery by horizontal, partial wedge resection of diffuse lesions, and total excision of small circumscribed lesions; --adjunctive therapy, which includes reduction of sharp incisal edges, early orthondontic therapy for open bite, and orthognathic surgery, if indicated.


Continued growth of a torus palatinus.

Continued growth of a torus palatinus.


A prototype articulator for planning orthognathic and craniofacial surgery. Current techniques and hinge-type articulators do not provide sufficient information and versatility for the planning of orthognathic and craniofacial surgery. Dental articulators either require plaster of paris for mounting or they do not accommodate movement of both casts in all directions of space. A prototype articulator that satisfies movement of both casts in all directions of space is successfully being used as an adjunct in planning orthognathic and craniofacial surgery. There is a need for future development of sophisticated and accurate armamentarium that can be used as an aid in planning and designing surgical procedures.


Cobalt radiation to prevent reankylosis after repeated surgical failures: report of case. This is the first reported case of the use of cobalt 60 radiation for the prevention of recurrent TMJ ankylosis after repeated surgical treatment had failed. Although radiation therapy is not usually indicated for benign conditions, 2,000 rads can be used safely to treat this crippling condition. Although no conclusions can be drawn from a single case, successful treatment of this patient is indicated by a 3 1/2-year follow-up.


Arteriovenous malformation: a five-year follow-up.


Periodontosis: incidence and findings in a military population.


Dental care for the geriatric indigent.

Dental care for the geriatric indigent.


Disseminated herpes simplex with hepatoadrenal necrosis in a child with acute leukemia.


The use of biofeedback to control bruxism. A highly significant reduction in bruxism has been obtained using a biofeedback system. The concept that the etiology of bruxism is related to emotional stress is supported as biofeedback has been successful in controlling other stress-related parameters. The form of biofeedback used as an audible tone derived from amplified electromyographic data, relayed to the subject via an earpiece. Future work will be concerned with learning potential and the control of parafunctional activity; further investigation into the correlation between E.E.G. patterns and masticatory E.M.G. activity is necessary.


The treatment of myofascial pain-dysfunction syndrome using the biofeedback principle. Facial pain is a relatively common sequel to bruxism and the biofeedback principle was used on seven subjects experiencing this syndrome. The results obtained were satisfactory and support the concept that the etiology of the M.P.D. syndrome is psychophysiological. This study showed that biofeedback is both a logical and appropriate form of treatment. However, the result with subject 7 indicates that not all patients are willing to wear the equipment but conselling and empathy probably form an equally satisfactory form of treatment.


Prolongation of antibacterial activity of chlorhexidine adsorbed to teeth. Effect of sulfates. The results suggest that the effectiveness of sulfates in prolonging the antibacterial activity of teeth treated with chlorhexidine gluconate is related to the acidity and concentration of the sulfate solutions. The acidity may contribute to the effectiveness by modifying the tooth surface for enhanced reaction with sulfate ions. It is suggested that during the priming process bonded crystals of calcium sulfate develop which become transformed by treatment with chlorhexidine gluconate to relatively insoluble chlorhexidine sulfate.


The effects of hypophysectomy upon DNA synthesis in rat oral epithelium. Ten hypophysectomized and 10 normal female albino rats, 50-days-old, were kept for 5 days and treated with tritiated thymidine 1 hour before sacrifice of the animals. The animals were weighed and the histomorphology of the palate epithelium was studied including the thickness, cell density, and DNA labeling index. The hypophysectomized rats failed to gain weight after 5 days. The palatal epithelium showed a normal morphology indicating the hypophysectomy allowed for differentiation of squamous epithelium. There was a significant reduction in the thickness of the epithelium and a reduced cell density. This was attributed to a significant decrease in DNA synthesis. The epithelial cells were lost from the surface without adequate replacement due to an expected depression in mitotic activity. DNA synthesis may be depressed due to reduced ATP synthesis resulting from suboptimal glucose metabolism and depression in protein synthesis.


Nutritional evaluation of food intake records of periodontal patients. The nutrients in 5-day diet diaries of 100 patients from an Iowa private dental office were analyzed with the assistance of a computer program and were compared to the RDA. The mean energy intakes of both men and women were lower than that suggested by the RDA's. The percent of kilocalories of fat was as high as the national average. Calcium was below 100% of RDA for both younger and older men and women with 43% of the women and 25% of the men below two-thirds of RDA. Protein and ascorbic acid levels were high. None of the diets were low in protein. The ascorbic acid intake was especially high, older men eating an average of 248% and older women 265% of RDA. Nutrient analysis of diets is more definitive than the commonly used food group plan for the dentist to meet the needs of nutrition counseling for an increasingly nutrition-conscious patient population.


Palatal exostosis in the molar region.

Palatal exostosis in the molar region. Six hundred and eithty-one dried human skulls of different ethnic backgrounds or localities were examined for the presence of palatal exostosis in the molar region. Of these samples, 276 (40.53%) exhibited some form of palatal exostosis. Chi-square analysis shows that the occurrence of exostosis is: (a) Dependent upon the locality in which the subject lives; (b) Influenced by age; (c) In any age group, dependent upon the locality; (d) Dependent upon the type or class of exostosis; (e) In any type, influenced by locality. The result of this investigation may become clinically important. It suggests, for the clinicians in the field of periodontics, certain diagnostic guidelines for treatment planning of periodontal surgical procedures in the palatal molar region. Thus, an awareness of the patients' ethnic background, as well as age, may be essential in order to minimize or avoid unnecessary postoperative healing complications.


Calcium hydroxide and potassium nitrate as desensitizing agents for hypersensitive root surfaces. The purpose of this investigation was to evaluate calcium hydroxide and potassium nitrate individually as densensitizing agents for hypersensitive root surfaces. The apparatus used in the experiment to measure hypersensitivity was (a) a thermo-electric stimulating device to measure hot and cold stimulation quantitatively and (b) a mechanical stimulating device to measure scratch stimulation quantitatively. The conclusions drawn from the study were: 1. Calcium hydroxide was more consistently effective in decreasing sensitivity then was potassium nitrate or the control. 2. Calcium hydroxide as compared to the control was statistically (99% level of significance) more effective in reducing sensitivity to mechanical, hot and cold stimulation immediately and at the conclusion of the experiment (3 months). 3. It appears that calcium hydroxide could be used as a desensitizing agent initially following periodontal surgery to reduce pain from hypersensitive roots in order that proper oral hygiene could be reestablished.


A scanning electron microscopic study of the healing of free gingival grafts. 1. Gingiva from the buccal surfaces of the mandibular first molars was grafted to the alveolar mucosa of each of the three premolars in six adult Beagle dogs. Biopsies were made at 0,2,3,4,5,6,7,8,10,14,21 days and at 1 and 6 months. 2. The specimens were fixed in 2% glutaraldehyde, buffered with cacodylate, pH 7.4, rinsed in buffer, dehydrated in graded alcohols, critical point dried, coated with gold palladium alloy and viewed in an AMR-1000 SEM at a tilt of 20 to 25 degrees and an accelerating voltage of 20 kv. 3. The results of this study parallel those reported on the basis of light microscopic studies. The three-dimensional visualization of the graft shows that the external layer of epithelium degenerates and desquamates, except for the basal layer and the structural architecture of the connective tissue is not as well organized. 4. By 21 days the graft is essentially healed, both clinically and histologically.


The effect of periodontal dressing on supragingival microorganisms.


Plaque removal by the Bass and Roll brushing techniques. The effectiveness of plaque removal using two brushes with the Bass technique and two with the Roll method was compared in a group of 38 junior dental students using a crossover experimental design. The Bass technique was superior to the Roll method in cleaning the tooth tissue adjacent to the gingival tissue on the lingual and facial aspects, but no significant differences were found in the overall effectiveness. Cleaning of all tooth surfaces was at an unacceptable level and it is concluded that efficient tooth cleaning is not achieved by detailed instruction at a single visit including a demonstration of competence by the subject and the issue of written instructions. Repetition of the instruction within 3 weeks did not achieve a higher standard of plaque removal.


Importance of filament diameter when using bass brushing technique. A comparative study using a crossover experimental construction was made of the effectiveness of brushes containing 6/10 nylon filaments of 0.132 mm mean diameter using a Bass technique with those containing filaments of the same type of nylon but 0.280 mm diameter. Each type of brush was used for a 2-week period. Even though the finer filament brushes contained more than three times as many filaments, they were inferior in cleaning achievement to the brushes with the broader filaments. The difference was particularly marked on the facial aspect, but was largely nullified lingually. The effectiveness of the Bass technique in the gingival zone demonstrated in a previous investigation when brushes containing filaments of 0.18 and 0.20 mm were used, was not found in this investigation. It is concluded that filament diameter is critical in achieving effective cleaning using the Bass technique.


The retrocuspid papilla: hypothesis of origin.


The advantages of xeroradiography for panoramic examination of the jaws and teeth. Xeroradiography is an electrostatic imaging method which was significant advantages over conventional radiographic techniques. This article introduces the use of xeroradiography for panoramic examination of the jaws. The resultant images not only contain superior local contrast and detail when compared to conventional panoramic radiographs but also correlate well with histopathologic changes. The investigation indicates that xeroradiography is an important new diagnostic tool for detection of disease of the jaws and teeth.


Osteosarcoma: an example of the thickended periodontal ligament space. A case of osteosarcoma which displayed a widened PDL space in a dental radiograph was presented. Other causes for thickening of the PDL were reviewed and differentiated from the features seen in osteosarcoma.


Repair potential of the soft tissue-root interface.


Pulpal periodontal disease.

Pulpal periodontal disease.


Reviewing the literature relating to free gingival grafts.


An improved diagnostic point to aid in radiographic interpretation.


Periodontal emotional stress syndrome.

Periodontal emotional stress syndrome.


The effect of prolonged inactivity upon the contraction characteristics of fast and slow mammalian twitch muscle. 1. Prolonged inactivity of soleus (slow twitch) and medial head of flexor digitorum longus (fast twitch: previously commonly known as flexor hallucis longus and hereafter referred to as FDL) muscles of the cat was produced by sodium pentobarbitone anaesthesia or spinal isolation. Isometric contraction characteristics were examined after 4-22 days and 8-49 days respectively.2. Sleep of up to 3 weeks' duration was associated with progressive changes in the weight, maximum tetanic tension, speed of contraction and absolute refractory period of fast twitch muscle. The slow muscle showed corresponding changes which were not so pronounced. Cord isolation resulted in similar changes which tended to be reversed after longer periods of disuse.3. Fast muscle frequently exhibited an after-contraction with corresponding electromyographic activity following two weeks or more of disuse.4. The time to peak of FDL was prolonged, becoming approximately one and a half times normal. In contrast to other reports of disuse, that of soleus was normal or slightly prolonged.5. The ratio of twitch to tetanic tension of FDL increased to twice the normal value or greater and remained high. The soleus muscle showed a smaller increase with evidence of a return towards normal after longer periods of inactivity.6. Absolute refractory period of FDL was considerably prolonged (more than 50%) following barbiturate sleep and this also occurred, but to a lesser degree, with soleus after 4-7 weeks of cord isolation.7. The observation that inactivity produced slowing rather than an increased speed of switch contraction indicates that aggregate activity is not the controlling factor. Changes seen in the contraction characteristics of FDL are noted to show a general similarity to those occurring following denervation.


The relationship of vertical dimension of atypical swallowing with complete dentures. A number of subjects were studied cineflourographically during swallowing, and their vertical dimensions of occlusion were clinically evaluated. The subjects who had reduced vertical dimensions of occlusion were older than those with normal vertical dimensions, their dentures were older, their total years with complete dentures were more, and the tendency to swallow without opposing tooth contact was greater. The cumulative evidence indicates that such aberrant muscle activity might contribute to the regressive changes found in complete denture wearers.


Prosthetic management of patients with pemphigus vulgaris.


Acquired mesio-occlusion in adults: treatment without appliances. 1. The two types of mesio-occlusion are developmental (true Class III) and acquired. 2. In acquired mesio-occlusion the mandible can be retruded comfortably so that maxillary and mandibular incisors meet edge to edge. This cannot be done by the patient with developmental mesio-occlusion. 3. The extent and severity of periodontal disease cannot be predicted from the severity of the malocclusion. 4. In most patients the treatment of choice for acquired mesio-occlusion is coronal reshaping and periodontal therapy if periodontal disease is present. 5. Orthodontic therapy may be used as an adjunctive therapy in selected patients. However, disadvantages are often greater than advantages when orthodontic therapy is used to treat acquired mesio-occlusion in adults.


Occlusal adjustment for a physiologically balanced occlusion. An investigation of the neuromuscular effects of dental contact at the physiologic median occlusal position was conducted before and after occlusal adjustments. Eighteen patients with histories of functional disturbances of the masticatory system, but whose painful symptoms had subsided, were analyzed before and after occlusal adjustments. Nine of the patients with missing teeth received fixed partial dentures and occlusal adjustments. Another group of nine subjects with normal occlusions were used as controls. Electromyographic recordings of the bilateral temporal and masseter muscles enabled quantification of two reflex parameters, the EMG silent period duration, and the mechanical latency of the jaw-opening reflex. Phase-plane traces of jaw-closing velocity as a function of position displayed the repeatability of the median occlusal position. The statistical analysis disclosed that the mean duration of EMG silent periods and latency of the jaw-opening reflex were significantly reduced following the treatment procedures. Within the limits of this study it was concluded that the described occlusal adjustments will reduce the masticatory reflexes evoked at median occlusal position to within the range of normal subjects. Furthermore these changes can be monitored by electrophysical methods.


Arch length.

Arch length.


Fluoride supplements for infants and preschool children.


Biologic laws governing functions of muscles that move the mandible. Part IV. Degree of jaw separation and potential for maximum jaw separation. Accurate diagnosis and treatment of the gnathostomatic system require an understanding of both its biomechanics and its physiology. Clinically, the treatment consists of modifying the existing occlusal program to relieve stress from distressed tissues. The objective of treatment is to effect a neuromuscular release of the mandible. This may be accomplished by (1) equilibration of the natural occlusion, (2) orthodontics, (3) restorative procedures, or (4) surgery. Most frequently, however, the treatment entails some combination of these procedures. The criteria for success of treatment are not determined by the method or technique employed but by the neuromuscular response that the treatment produces. The purpose of this article is not to suggest which occlusal scheme produces the most favorable muscle response in the gnathostomatic tissues. Neither is an objective of this article to teach the mandible-manipulation techniques that are needed to identify occlusal irritants, perform occlusal equilibrations, or obtain accurate centric relation recores. The objective of this article is to emphasize that there are definite principles by which the muscles respond to occlusal contacts. Occlusal contacts can excite bruxism and the sequelae to bruxism. Knowledge of the laws which govern functions of the muscles that move the mandible enables the dentist to acquire the mandibular-manipulation skills that are necessary for the effective diagnosis and treatment of occlusal conditions.


Early rehabilitative management of the maxillectomy patient.


Rare earth imaging in dental radiology.

Rare earth imaging in dental radiology.


Evaluation of polymeric materials for maxillofacial prosthetics. The methods for initial evaluation of a new prospective maxillofacial prosthetic material, MDX-4-4210, have been described and tensile and compressive test data have been obtained. Evaluation of the data indicates that this is a promising material with significant potential for use in maxillofacial prosthetics. Further studies of the material's biologic implant compatibility, its chemical and environmental stabilities, and its clinical performance are being done.


Comparison of Myo-Monitor centric position to centric relation and centric occlusion. Twenty dentulous subjects were selected at random. A Hight tracer, fixed on the labial surface of the teeth by special clutches, was used to indicate a record of centric relation and centric occlusion. The Myo-Monitor centric position was recorded and compared to centric occlusion and centric relation in anteroposterior and lateral dimensions. This study indicated that: 1. Myo-Monitor centric position is always anterior to centric relation, with an average of 3.8 min. 2. Myo-Monitor centric position is always anterior to centric occlusion, with an average of 1.8 mm. 3. In 18 of 20 subjects, the Myo-Monitor registration was to the right or to the left side of the line between centric relation and centric occlusion. 4. In all subjects, centric occlusion was an average of 2.2 mm. anterior to centric relation.


Denturism--we must make an ethical choice.


Clinical management of denture-induced inflammations.


The adaptation of new amalgam and composite resins to pins.


Viscosity of elastomeric impression materials. (1) Some elastomeric impression materials (Omniflex and Impregum) exhibited extreme shear thinning properties. This property was considered useful and these materials can be considered all-purpose. (2) The use of impression materials in syringing applications should not be precluded simply because the substances are thick or heavy during spatulation. A tenfold reduction in viscosity with increasing shear rate was found for three of the materials tested. (3) Viscosity characteristics of the impression rubbers were linked to filler content. (4) The viscosity rise during cross-linking was monitored for various impression products. It was found that each manufacturer's specifications of the length of time for syringing were relatively accurate.


The treatment of temporomandibular joint dysfunction: a retrospective study.


Comparison of the efficacy of a questionnaire, oral history, and clinical examination in detecting signs and symptoms of occlusal and temporomandibular joint dysfunction. A comparison of three methods of obtaining information relating to some TMJ signs and symptoms has been made. The taking of an oral history by this examiner was shown to be the least reliable. The acquisition of data by this verbal process is a clinically sophisticated and difficult medical procedure and a major source of error is the bias or preconception that a clinician brings to his observations. Far more effective was a written, self-administered patient questionnaire, which proved quite reliable in detecting the presence of some occlusal habits. This study indicates that the initial use of a self-administered patient questionnaire, even in the hands of an inexperienced dentist, will ensure that certain essential data are obtained and recorded and will result in the discovery that a substantial number of patients have signs and symptoms of occlusal and TMJ dysfunction. The most objective method is of course the direct clinical examination. A combination of these three methods of obtaining information is recommended as an important part of routine occlusal and TMJ examinations.


A study of occlusion as related to the Frankfort-mandibular plane angle. The relation of the Frankfort-mandibular plane angle (FMA) to naturally occurring occlusion groups was studied in 112 subjects. Occlusion types were categorized into four groups depending on the magnitude of first-molar contact on the working side. Percentage (frequency) of occurrence of occlusion groups were: disclusion, 17.9 per cent; delayed disclusion, 19.6 per cent; progressive disclusion, 8.9 per cent; and group function, 53.6 per cent. The mean FMA for the study sample was 25.68 degrees with a range of 13 to 40 degrees. Mean FMA's for the occlusion groups showed a progressive increase from disclusion (19.6 degrees) to group function (28.9 degrees). A statistical test, extension of the median, indicated a highly significant relation between occlusion groups and the FMA. Considering these results, an FMA determination provides a structure-function basis to consider in selecting a scheme for occlusal reconstruction and should be incorporated in the treatment planning procedure as a major adjunctive diagnostic tool. However, further research, focused upon the many variables that determine a type of occlusion, must precede the formulation of a set of "rules" for selection of occlusion.


Simplified stippling blocks for skin surface reproduction.


Porcelain shade stability after repeated firing and shade modification of porcelain restorations.


Mammographic diagnosis of gynecomastia.

Mammographic diagnosis of gynecomastia.


Management of infectious disease in pediatric practice.


Active tuberculosis in New Jersey.

Active tuberculosis in New Jersey.


Ruptured splenic artery aneurysm.

Ruptured splenic artery aneurysm.


Transient ischemia of the small bowel secondary to lupus vasculitis.


Pitfalls in the diagnosis of advanced abdominal pregnancy.


Cerumen as a lubricant.

Cerumen as a lubricant.


Are you aiding the denturist movement?

Are you aiding the denturist movement?


Periodontosis--general discussion and report of familial cases.


Sicca syndrome in a patient with toxic reaction to busulfan.


The management of metastatic carcinoma of the prostate.


Anesthetic management of a patient with osteogenesis imperfecta undergoing cesarean section.


Spontaneous rupture of the liver in pregnancy.


The Hampton project: initial census data for a community-based health communication system.


A synopsis of left ventricular performance.


Genetic counseling: helping the family.

Genetic counseling: helping the family.


New hue '77.

New hue '77.


Precedent-setting lawsuit won by dental laboratory.


Molecular basis for acquired haemoglobin H disease.


The university and dental education.

The university and dental education.


Suicide, divorce, and alcoholism among dentists, fact or myth?


Ethics, cancer and children.

Ethics, cancer and children.


Ethionine toxicity in the parotid gland.


Form, function and tooth position.

Form, function and tooth position.


Reflections.

Reflections.


President's report: P.O.H. (preserve our health).


Dentistry is in trouble.

Dentistry is in trouble.


Become a dentist, why?

Become a dentist, why?


Posterior fossa neurovascular decompression for tic douloureux and hemifacial spasm.


The physician's responsibilities to fill out the death certificate.


Presence of complement-fixing antibodies against antigens of Gross virus-induced rat lymphoma and normal rat thymus in sera of patients with some forms of malignancies. Presence of complement-fixing antibodies against soluble antigen(s) of Gross virus-induced rat lymphoma W/Fu(C58NT)D was determined in sera of 180 healthy donors, in sera from 100 healthy pregnant women and in sera obtained from 139 patients with acute myelosis, acute lymphadenosis, acute undifferentiated leukosis, chronic myelosis, chronic lymphadenosis and Hodgkin's disease. Antibodies against soluble complement-fixing antigen from W/Fu(C58NT)D rat lymphoma were found in 33 (5).5%) out of 64 sera of patients with acute leukemia, in 15 out of 60 sera of patients with Hodgkin's disease, in 17 (9.4%) out of 180 healthy donors and in 22 (22.0%) out of 100 sera from healthy pregnant women. None of 15 sera from patients with chronic leukemia were positive. Titers of complement-fixing antibodies in positive sera remained unchanged after absorption with pooled lymphocytes from healthy human donors. Some selected positive sera reacted also with a soluble antigen prepared from normal rat thymus. Nature of complement-fixing antibodies detected and of corresponding antigens is discussed.


Rules of the New York State Board of Regents relating to definitions of unprofessional conduct. Approved July 28, 1977, to be effective October 1, 1977.


Idiopathic resorption.

Idiopathic resorption.


The powerful placebo.

The powerful placebo.


Carcinoma of the lip.

Carcinoma of the lip.


Growth defects in unrepaired unilateral cleft lip and palate. The positional relationships of the dentoalveolar segments in ten subjects with unrepaired unilateral complete clefts of lip and palate were studied in order to assess the effects of the cleft malformation on dentoalveolar growth. The findings suggest that there are localized growth defects, particularly in lateral and vertical growth at the region of the alveolar cleft, which cannot be accounted for by operative trauma. The position and shape of the central incisor nearest the cleft was also found to be defective in some subjects.


Excision of buccal hemangioma by carbon dioxide laser beam. The carbon dioxide laser beam was used successfully to extirpate a large buccal hemangioma in a child. No hemostats were required, as this new surgical modality affords a practically bloodless operative field. Tissue necrosis occurs only minimally at the borders of the incision. Operative intervention with the carbon dioxide laser beam in cases of hemangioma and other tumors of the oral cavity is advocated.


Myositis ossificans traumatica of the masseter muscle. Report of a case. A case of myositis ossificans traumatica has been reported. Clinical, histopathologic, and roentgenographic entities have been referred to. An up-to-date review of the literature on this disorder has been presented.


From the president.

From the president.


Large-cell carcinoma metastatic to the jaw. Report of a case. A case of two metastatic lesions of the oral mucosa simulating odontogenic infections is presented. One lesion mimicked chronic pericoronitis, and the other lesion mimicked a dental abscess. The case stresses the need for routine biopsy and pathology examination of conditions found in the oral cavity.


An experimental evaluation of regionally induced analgesia in dentistry. A method for the assessment of induced regional dental analgesia in experimental animals is described. It is based on the validity of the electrodentally elicited digastric electromyogram as a pain index. This method has been applied to study the effectiveness of one local anesthetic and of "electroacupuncture" to suppress pain regionally.


Gadgets, gizmos, and junk.

Gadgets, gizmos, and junk.


Bacterial contamination and transmission by nitrous oxide sedation apparatus. Microbial contamination of sterile nasal hoods was demonstrated in nine of twenty-one clinical administrations of nitrous oxide-oxygen conscious sedation. In each case, bacteria isolated from the hood after 30 minutes' use were correlated morphologically with organisms recovered from the subject's nasal mucosa. A laboratory investigation utilizing an artificial respiration-sedation system revealed that there is a significant possibility of cross-infection between patients when improperly disinfected sedation equipment is employed.


Familial hypoparathyroidism with candidiasis and mental retardation. Five new cases of the syndrome of hypoparathyroidism, candidiasis, and mental retardation are described and the importance of the dental findings in contributing toward a definite diagnosis is stressed. The close consanguineous relationship of the parents, first cousins in all of these cases, makes imperative the consideration of the concept that the syndrome is a congenital defect, transmitted by a recessive gene.


Intraoral pemphigus vulgaris.

Intraoral pemphigus vulgaris. Twenty-eight cases of intraoral pemphigus vulgaris are presented. All had histologic confirmation, including twenty-six from intraoral biopsies. Detailed descriptions involving many clinical features are reported and discussed. Pertinent histologic findings are also described.


American Burkitt's lymphoma in Pittsburgh, Pennsylvania. A confirmed case of American Burkitt's lymphoma with jaw involvement in a 12-year-old Caucasian girl from western Pennsylvania is described. There were clinical manifestations in the mandibular quadrants and radiographic manifestations in all mandibular and maxillary quadrants. One of the earliest clinical manifestations of the lymphoma in the mandible was observed by a family dentist. The lymphoma later produced a deterioration of the overlying mandibular mucosa, moderate expansion of the cortex of the mandible, and paresthesia of the lip with probable V3 involvement. Four months after the first admission there were radiographic manifestations of the lymphoma in both the maxillary and mandibular quadrants. Early diagnosis and appropriate management may improve the prognosis.


NECROTIZING SIALOMETAPLASIA.

NECROTIZING SIALOMETAPLASIA. Nonhealing palatal ulcerations in two white male patients, one 50 and another 58 years of age, were clinically suspected of being malignant, even after the initial biopsies were negative. Second biopsies in each case confirmed the original opinions, but the lesions were diagnosed specifically as "necrotizing sialometaplasia". This is an interesting condition of uncertain etiology that can mimic cancer, both clinically and microscopically. The condition heals spontaneously. It should be considered in a differential diagnosis of suspicious lesions of the palate.


Tuberculous osteomyelitis of the mandible. An unusual case of tuberculous involvement of the mandible in a 22-month-old African girl is presented. Other tissues involved included the small bones of the hands and feet and pulmonary, cervical, and submental lymph nodes. A short discussion of the pathogen involved is offered.


An electron microscopic study of collagen formation in the dental pulp of the human premolar and rat incisor. Collagen secretion and maturation were investigated at the ultrastructural level. Pulp tissue from the continuously growing incisor of the rat provided excellent material for studying the secretory aspects of the tropocollagen. More mature human pulp material proved valuable in viewing the collagen fibril. A networklike arrangement of fibroblasts and fibrocytes was noted. Various types of cell junction were found in all specimens. The finding of a nexus junction was particularly interesting. It is hypothesized that connected cell systems rather than single cells might be the functional units involved in collagen formation.


Endodontic morphology. I. An alternative method of study. Several techniques have been reported for the demonstration of canal systems in vitro. An additional technique has been developed which allows for the study of the internal anatomy of teeth prior to and after instrumentation on the same specimens. The use of a water-soluble contrast medium infused into root canal systems provides for easy removal of the contrast medium without alteration of the internal anatomy of the teeth. The pulps were eliminated from 164 extracted human teeth by enzyme action; the pulp chambers and root canal systems were filled under vacuum with a water-soluble, radiopaque contrast medium; and each tooth was radiographed from three angles with the contrast medium in situ. The contrast medium was cleared and an additional radiograph was taken. The potential for this procedure in the evaluation and assessment of the technique of canal preparation has been projected.


Evaluation of endodontic instruments as received from the manufacturer: the demand for quality control. Two hundred seventy new files, reamers, and Hedström files from three different manufacturers were evaluated for debris and defects. Statistical analysis of the new instruments showed that one company's instruments were cleaner than the other two but still contained defects. A standard for quality is proposed.


Analysis of interpretations of full-mouth and panoramic surveys. The purposes of this study were to determine differences in interpretation of radiographic findings of full-mouth and panoramic surveys by junior and senior dental students and differences in their interpretive skills. The parameters of interest were caries, incipiencies, lamina dura interruptions, periodontal membrane changes, and periapical bone changes. The questions to be answered regarding the differences between the full-mouth and panoramic surveys were: (1) In which type of radiograph were the most lesions found? (2) In which type of radiograph are the most "non-existing" lesions found? (3) In which type of radiograph are the most lesions undetected? (4) Does the junior or senior dental student demonstrate the most accuracy in his interpretation?


Radiographic observations of pyknodysostosis. Report of a case. A case of pyknodysostosis in a 32-year-old woman has been reported. The patient presented typical skeletal changes, separated cranial sutures, open fontanelles, partial aplasia of the terminal phalanges of the fingers and toes, and brachyphalanges. The oral findings included lesions resembling periapical cementoma, hypoplasia of the maxilla and mandible, crowding of teeth, and a median raphe.


Foreign objects in the root canal. Review of the literature and report of two cases. In the two cases reported here, the foreign object in the child's tooth was not the specific reason for seeking treatment. When the presence of the objects was ascertained, neither parent could recall any mention being made by the child of introduction of the foreign body.


Aberrant canal to mandibular third molar area.


A dentigerous cyst originating from a mandibular second premolar.


Leaded apron artifact on panoramic radiograph.


Rapid bone regeneration subsequent to subtotal mandibulectomy. Report of an unusual case. An unusual case of rapid bone regeneration after resection of a large portion of the mandible is presented. The possible factors responsible for the bone regeneration are discussed, with emphasis on the age of the patient, preservation of the periosteum, and infection.


Antineoplastic agents and their oral manifestations. The use of antineoplastic agents is rapidly increasing. A general classification of these drugs and their mechanisms of action is presented. Many of the drugs have an adverse effect on oral tissue, and the practicing dentist today must be well acquainted with these effects. A discussion of the features of these reactions and their management is presented.


Maxillary chondrogenic sarcoma: management of a case.


Ultrastructural study of hereditary benign intraepithelial dyskeratosis. Specimens taken from the buccal mucosa of two patients with hereditary benign intraepithelial dyskeratosis (HBID) were studied with the transmission electron microscope. Ultrastructural features were described and compared with those of white sponge nevus and Darier's disease. Ultrastructural findings in HBID revealed the presence of numerous vesicular bodies in immature dyskeratotic cells, densely packed tonofilaments filling the cytoplasm of mature dyskeratotic cells, and the disappearance of cellular interdigitations and desmosomes in mature dyskeratotic cells.


Dentin dysplasia, type II: a rare autosomal dominant disorder. Dentin dysplasia, Type II, is a rare autosomal dominant disorder. The primary teeth are amber and translucent and the pulp chambers are obliterated. The permanent teeth have a normal to brown-gray coloration and a thistle-tube pulp configuration with multiple true denticles. To date, only five families with this disorder have been reported. This article presents two additional families. Light and scanning electron microscopy of an affected primary incisor showed the dentin, including the mantle layer, to be highly disorganized throughout. Possible pathogenic events associated with the phenotype are discussed.


Macrodontia of a mandibular premolar.

Macrodontia of a mandibular premolar.


Endodontic morphology. II. A radiographic analysis. Radiographs of 164 extracted human teeth were examined under magnification subsequent to the infusion of a radiopaque contrast medium under vacuum into their empty canal systems. An analysis of the results was made from the recorded statistics, and some conclusions have been drawn from these. The form and number of canals generally conformed to those of the roots which housed them, with some exceptions. The presence of two canals in the mesiobuccal roots of maxillary first molars and the incidence of lateral, accessory, and furcation canals have been noted. The role of the endodontist in the treatment of teeth with such anatomic features was discussed.


Focal infection in perspective.

Focal infection in perspective. In this article some of the theoretical possibilities arising as a result of focal infection are discussed. Rheumatic fever is discussed as an example of a disease in which a number of possible mechanisms may act to produce tissue damage at a target area. The mechanisms examined are direct dissemination of organisms from the focus to the target area, the induction of L-phase bacteria, and toxic damage to target tissue. Host-mediated tissue damage by hypersensitivity or auto-immune mechanisms is considered as well.


Focal infection--the endodontic point of view.


A study of human mandibular nutrient canals.


Evaluation of a technique for standardized periapical radiographs. A paralleling instrument with an orientation bite-block was designed to provide standardized projections on periapical radiographs with the extension cone paralleling technique. The reproducibility of root images on these radiographs and the relocation of the orientation bite-block in relation to root structures were tested in five patients. Three radiographs were subsequently made of each patient and compared. The projection error proved to be negligible.


Static bone cavity.

Static bone cavity.


A true "eye tooth".

A true "eye tooth".


Informed consent--records.

Informed consent--records.


Sued for death of patient, insurer must defend dentist.


Another Swiss roll...

Another Swiss roll...


Grant-in-aid. Why the GDPA has changed its policy.


A 'busman's rise' for dentists.

A 'busman's rise' for dentists.


AD win design award.

AD win design award.


Swiss: watch those flamboyant signs!

Swiss: watch those flamboyant signs!


No significant improvement in dental health.


Is this clinical freedom?

Is this clinical freedom?


New laws on women employees.

New laws on women employees.


Coordination of ribosome content and polysome formation during estradiol stimulation of vitellogenin synthesis in immature male chick livers. To elucidate the mechanisms by which protein synthesis is affected by estradiol, we characterized cockerel liver polysomal profiles during hormone induction and withdrawal. We describe a method for isolating intact polysomes which results in preparations that are stable even after storage in solution at 10 degrees for 16 hr. In addition, our procedure eliminates the necessity for starving animals prior to experiments. Recovery of radioactive polysomes indicated that yield is about 90% and that our polysomal preparations appear to represent polysome distribution in vivo. Using this approach we show that estradiol injection stimulates ribosome content 6-fold and that formation of polysomes is coincident with the induction of vitellogenin synthesis. We also demonstrate that the size and number of polysomes increase and decrease in a coordinated fashion with the rate of vitellogenin synthesis. The kinetics of ribosome synthesis and the fact that at least 80% of the newly synthesized ribosomes are directly recruited into polysomes indicate that ribosomes might be limiting the rate of protein synthesis during the stimulatory phase of the hormone cycle.


Primary structure of human C-reactive protein. The complete amino acid sequence of human C-reactive protein has been established. Distant homologies to C3 homology region in the CH2 domain of IgG and to C3a anaphylotoxin have been noted. No homology to other immunoglobulin homology regions or to the same homology region in other heavy chains was observed. The previously reported homologies between rabbit and human C-reactive protein and protein C1t have been extended and strengthened.


Uterine peroxidase as a marker for estrogen action. Administration of a single dose of estradiol to immature rats gives rise to the appearance of substantial amounts of peroxidase (donor:hydrogen-peroxide oxidoreductase, EC 1.11.1.7) enzyme activity in the uterus. This enzyme induction, which is inhibited by administration of actinomycin D and cycloheximide, can be detected at 4 hr after administration of estradiol, reaches a maximum level by 20 hr, and thereafter declines. The amount of uterine peroxidase seen at 20 hr after a single dose increases with dose from 0.1 to 100 microgram of estradiol. Estrone and estriol also show dose-dependent induction of peroxidase, and the quantitative peroxidase responses to these steroids follow their uterotropic capacities. The antiestrogen CI628, capable of low levels of enzyme induction by itself, can inhibit the induction due to estrogen. Solubilization of the uterine enzyme with divalent cations, especially calcium, results in a substantially increased yield of peroxidase. This extraction method provides an enzyme of about 50,000 molecular weight in distinction to the large aggregated form obtained by the usual extraction with sodium chloride.


Spliced segments at the 5' terminus of adenovirus 2 late mRNA. An mRNA fraction coding for hexon polypeptide, the major virion structural protein, was purified by gel electrophoresis from extracts of adenovirus 2-infected cells late in the lytic cycle. The mRNA sequences in this fraction were mapped between 51.7 and 61.3 units on the genome by visualizing RNA-DNA hybrids in the electron microscope. When hybrids of hexon mRNA and single-stranded restriction endonuclease cleavage fragments of viral DNA were visualized in the electron microscope,branched forms were observed in which 160 nucleotides of RNA from the 5' terminus were not hydrogen bonded to the single-stranded DNA. DNA sequences complementary to the RNA sequences in each 5' tail were found by electron microscopy to be located at 17, 20, and 27 units on the same strand as that coding for the body of the hexon mRNA. Thus, four segments of viral RNA may be joined together during the synthesis of mature hexon mRNA. A model is presented for adenovirus late mRNA synthesis that involves multiple splicing during maturation of a larger precursor nuclear RNA.


Tumorigenicity of five dihydrodiols of benz(a)anthracene on mouse skin: exceptional activity of benz(a)anthracene 3,4-dihydrodiol. Benz[a]anthracene and the five metabolically possible vicinal trans dihydrodiols of benz[a]anthracene were tested for ability to initiate skin tumors in CD-1 female mice. A single topical application of 0.4-2.0 mumol of hydrocarbon was followed 18 days later by twice weekly applications of the skin promoter 12-O-tetradecanoylphorbol-13-acetate. Comparisons of latency period, percent of mice with tumors, and number of papillomas observed per mouse indicated that benz[a]anthracene 1,2-, 5,6-, 8,9-, and 10, 11-dihydrodiols were all less active tumor initiators than was benz[a]anthracene. The high tumorigenicity of benz[a]anthracene 3,4-dihydrodiol, presumably the result of metabolism to either or both of the diastereomeric benz[a]anthracene 3,4-diol-1,2-epoxides, supports the bay region theory of polycyclic hydrocarbon carcinogenicity and provides the first example of a proximate carcinogenic metabolite that is much more active than the parent hydrocarbon on mouse skin.


Identification and cloning of the chloroplast gene coding for the large subunit of ribulose-1,5-bisphosphate carboxylase from Chlamydomonas reinhardi. mRNA coding for the large subunit (LS) of ribulose-1,5-bisphosphate carboxylase [3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39] from Chlamydomonas reinhardi has been isolated from small polyribosomes immunoadsorbed to column-bound anti-LS antibody. 32P-Labeled LS mRNA was used as a hybridization probe to detect LS genes. The probe hybridized to C. reinhardi chloroplast DNA and at hybridization saturation revealed that there are approximately 75 LS genes per chloroplast. When chloroplast DNA was digested with the restriction endonuclease EcoRI and the fragments were transferred to a nitrocellulose filter, the LS mRNA probe hybridized to a DNA fragment of molecular weight 3.2 X 10(6). This same fragment codes (in part) for 16S and 23S chloroplast rRNAs, which are also coded (in part) by fragments of molecular weights 9.0, 2.3, and 0.4 X 10(6). The restriction fragment containing the LS gene has been cloned in the Escherichia coli plasmid pMB9.


phiX174 cistron A protein is a multifunctional enzyme in DNA replication. The cistron A protein induced by phage varphiX174 nicks (produces a single-strand break in) the viral strand of the superhelical varphiX duplex DNA, thereby forming a complex with the DNA. The protein, seen bound to the DNA in the electron microscope, was located in the restriction endonuclease fragment between nucleotides 4290 and 4330 on the varphiX map [Sanger, F., Air, G. M., Barrel, B. G., Brown, N. L., Coulson, A. R., Fiddes, J. C., Hutchison, C. A., III, Slocomb, P. M. Y. & Smith, M. (1977) Nature 265, 687-695]. Replication also was initiated at this point, thus identifying the site of cistron A protein nicking and binding as the origin of replication. The cisA-DNA complex (separated from free cistron A protein), upon the addition of Escherichia coli rep protein, ATP, and DNA binding protein, is unwound to generate a single-stranded linear [presumably the nicked (+) strand] and a circular [presumably the (-) strand] molecule. The cisA-DNA complex, upon the further addition of DNA polymerase III holoenzyme and deoxynucleoside triphosphates, supports replication to generate viral, single-stranded circles, as many as 15 circles per cisA-DNA complex. The replicating intermediates seen in the electron microscope are a novel form of "rolling circle" [Gilbert, W. & Dressler, D. H. (1969) Cold Spring Harbor Symp. Quant. Biol. 33, 473-485]. The 5' end (presumably with the cistron A protein bound to it) is locked in the replication fork and loops back to accompany the strand-separation and replication fork around the template [(-) strand] circle. Thus, the multiple functions of cistron A protein include: (i) nicking the viral strand at the origin of replication to initiate a round of replication, (ii) participating in a complex which supports fork movement in strand separation and replication, (iii) nicking again at the regenerated origin to produce a unit-length DNA, and (iv) ligating the newly generated 3'-OH end to the 5'-phosphate-complexed end to form a circular viral molecule.


Cleavage specificity of the restriction endonuclease isolated from Haemophilus gallinarum (Hga I). The nucleotide sequences in the replicative form (duplex) of phiX174 DNA around six sites cut by Hga I, a restriction endonuclease from Haemophilus gallinarum, have been compared. The enzyme produces a staggered cleavage resulting in a pentanucleotide 5'-terminal extension. The sequences within and immediately surrounding the pentanucleotide cleavage site have no obvious relationship. However, the sequence 5'-G-A-C-G-C-3'  3'-C-T-G-C-G-5' occurs five nucleotide pairs to the left of the cut in the upper strand and 10 nucleotide pairs to the left of the cut in the lower strand and, therefore, is believed to constitute the recognition site. This is a member of the class of restriction endonucleases in which recognition and cleavage sites lack 2-fold rotational symmetry. The method used to define the cleavage site is of general applicability.


Identification of beta,beta-turns and unordered conformations in polypeptide chains by vacuum ultraviolet circular dichroism. Different conformations of polypeptides were characterized by measurements of the circular dichroism (CD) extended into the vacuum ultraviolet region. (i) The linear beta-pleated sheet structure was characterized in a broad ultraviolet region down to 165 nm by examination of copolypeptides composed of alternating hydrophobic and hydrophilic amino-acid residues, e.g., poly(Lys-Leu-Lys-Leu). A short-wavelength intense band was found at about 169 nm, which is characteristic of beta-pleated sheet conformation. (ii) The beta-turns were experimentally measured using poly(Ala(2)-Gly(2)) in a broad spectral region down to 165 nm with accuracy. The observed CD spectrum is in excellent qualitative agreement with the theoretical curve calculated by Woody for the beta-turns of type II and/or I of Venkatachalam. The similarity in shape between the theoretical curve and the observed CD spectra suggests a dominance of beta-turn segments in the poly(Ala(2)-Gly(2)) structure. The presence of beta-turns in poly(Ala(2)-Gly(2)) is also in agreement with the characterization of this polypeptide by solid state methods (electron microscopy and x-ray diffraction). The CD spectrum of beta-turns is characterized by a very intense band at 207.5 nm and strong negative bands at 191 and 169 nm. Copolypeptides such as poly(Ala(2)-Gly(3)) and poly(Ala(3)-Gly(3)) yielded a similar type of CD spectrum, analysis of which indicates that a large fraction of their residues is contained in beta-turn regions. (iii) The CD spectrum of the unordered chain of these alternating copolypeptides in salt-free solution is observed in the vacuum ultraviolet region.


Conformation of beta-endorphin and beta-lipotropin: formation of helical structure in methanol and sodium dodecyl sulfate solutions. Circular dichroic spectra of camel beta-endorphin and ovine beta-lipotropin in water show little, if any, secondary structure. Intrinsic viscosities and sedimentation coefficients of the two peptides also suggest that the molecules are not compact and globular. Methanol or sodium dodecyl sulfate promotes the formation of helical structure to an extent as much as one-half of either peptide molecule. The conformation of the complex between camel beta-endorphin and dodecyl sulfate may be related to the opiate-like function of this peptide hormone.


Physical properties of chemically acetylated rat liver chromatin. The physical properties of rat liver chromatin and nucleosomes acetylated with acetic anhydride were examined in order to clarify the mechanism by which chemical acetylation of histones increases template activity in vitro [Marushige, K. (1976) Proc. Natl. Acad. Sci. USA 73, 3937-3941]. Acetylation was found to have dramatic effects on the magnesium solubility, nuclease sensitivity, thermal denaturation, and sedimentation of chromatin and nucleosomes. The significance of the results to models of gene activation and chromatin replication is considered.


5'-Terminal 7-methylguanosine and mRNA function: influence of potassium concentration on translation in vitro. Vaccinia mRNAs containing either 5'-terminal m7G or unmethylated 5'-terminal structures were synthesized in vitro and their relative efficiencies of translation were compared in wheat germ and reticulocyte cell-free protein-synthesizing systems. The importance of the m7G group for efficient translation increases as the K+ concentration is raised. At K+ concentrations optimal for translation of mRNA containing m7G, unmethylated mRNA is translated at the same relative low efficiency in both cell extracts. The rate of binding of mRNA to ribosomes at K+ concentrations close to those found in intact cells is strongly influenced by the presence of m7G regardless of the source of the cell extract.


Conformational alteration of protein synthesis elongation factor EF-Tu by EF-Ts and by kirromycin. Alterations of the structure of EF-Tu have been investigated by using the rate of EF-Tu cleavage by trypsin as a conformational probe. The presence of EF-Ts bound to EF-Tu results in a 10-fold increase in the cleavage rate. The antibiotic kirromycin, which inhibits protein synthesis by virtue of its interaction with EF-Tu, mimics this effect of EF-Ts. Both kirromycin and EF-Ts also facilitate the exchange of free GDP with GDP bound to EF-Tu. The results suggest that EF-Ts and kirromycin induce a similar conformational change in EF-Tu, thereby "opening" the guanine nucleotide binding site. The trypsin-cleaved EF-Tu still can bind GDP and EF-Ts and can function in Qbeta replicase, but it no longer spontaneously renatures following denaturation in urea.


Identification of synaptic acetylcholine receptor sites in retina with peroxidase-labeled alpha-bungarotoxin. An alpha-bungarotoxin-horseradish peroxidase conjugate, which binds specificity to nicotinic acetylcholine receptors, was synthesized. This conjugate was bound by 5-7% of the synapses in the inner plexiform layer of the chicken retina. Bipolar ribbon synapses as well as amacrine synapses bound the conjugate.


Synthesis of human interferon by Xenopus laevis oocytes: two structural genes for interferons in human cells. Human fibroblasts and leukocytes produce interferons which may be distinguished by their antigenic and species specificity as well as by their molecular weight distributions. To elucidate the basis for these differences, we isolated mRNA from induced human fibroblasts and lymphoblastoid (Namalva) cells and studied the products of translation in Xenopus laevis oocytes. The mRNA from the respective cells yielded translation products, in oocytes, that were characteristic of the cells from which the mRNA was derived. We conclude that human cells contain at least two structural genes for interferon, coding for polypeptides differing in primary sequence. Fibroblasts synthesize a single species of interferon; lymphoblastoid cells synthesize two species, the fibroblast and leukocyte types.


Subunit structure of chromatin and the organization of eukaryotic highly repetitive DNA: nucleosomal proteins associated with a highly repetitive mammalian DNA. Component alpha DNA is a homogeneous, highly repetitive fraction that comprises nearly a quarter of the African green monkey (Cercopithecus aethiops) genome. By restriction enzyme analysis, it has a repeat periodicity of 176 +/- 4 nucleotide base pairs, corresponding closely with the length of DNA contained within a nucleosome. The sequence is organized into large blocks of constitutive heterochromatin. A method is described here for the isolation of intact polynucleosomal arrays containing only component alpha sequences. Isolated monkey nuclei are treated with EcoRI, which releases only component alpha nucleosomal arrays; the arrays are then fractionated and purified by sedimentation in sucrose gradients. The method permits a compositional analysis of the proteins associated with a constitutively repressed, heterochromatic sequence. The major differences in the proteins associated with component alpha nucleosomes that distinguish them from the bulk DNA nucleosomes are a decrease in the content of the H1 histones in the component alpha nucleosomes and a concomitant increase in the amount of certain nonhistone proteins. The specific observations are: (i) In the component alpha nucleosomes, 65-70% of the proteins were nonhistone proteins; this contrasts with the value, 40%, for nonhistone proteins associated with nucleosomes containing bulk DNA. (ii) The amount of H1 histone in chromatin containing predominantly bulk DNA was about 13.7%. However, the H1 histone was depleted and possibly absent in component alpha oligonucleosomes. (iii) Coincident with the decrease in the H1 histones and in the same molecular weight range (24,000-43,000), there appeared five minor nonhistone proteins. The minor, low-molecular-weight, nonhistone proteins were not detected in chromatin containing bulk DNA but they represented nearly 12% of the protein in component alpha nucleosomes. The resistance to salt extraction (0.6-2.0 M NaCl) indicates that the low-molecular-weight nonhistone proteins are tenaciously bound to the component alpha nucleosomes. In addition, a class of high-molecular-weight (>100,000) nonhistone proteins was enriched 5- or 6-fold in component alpha oligonucleosomes. The relative amounts of the nucleosome core histones were not changed.


Kinetics of processing of type I and type III procollagens in fibroblast cultures. The rates of conversion of types I and III procollagens to their respective collagens were compared in seven fibroblast culture systems of murine or human origin. During 24 hr of radioactive labeling or after shorter pulses followed by chases of 20-48 hr, no evidence was obtained for conversion of radiolabeled type III procollagen to insoluble collagen. In the same cultures and under the same conditions, native collagen was generated from radiolabeled type I procollagen. There was no evidence for proteolytic degradation of type III procollagen during the chase experiments. The results are ascribed to a lack of availability of the enzymes required for processing of type III procollagen.


Thermodynamics of the self-association of glucagon. In water, glucagon exists in an equilibrium between a trimer in which more than half of the peptide groups are in an alpha-helical configuration and a monomer which has a random coil configuration with few alpha-helical residues. The thermodynamics of this self-association have been evaluated by studying the temperature- and concentration-dependence of the mean residue ellipticity at 220 nm. The enthalpy and entropy changes of association were negative at all temperatures between 5 degrees and 50 degrees and had large negative temperature dependencies. Usually an association that involves nonpolar groups is considered to be driven by a positive entropy term. Such an explanation is not tenable in the case of glucagon. However, if the effects of nonpolar groups on the coil-to-helix transition of a polypeptide are included into the thermodynamic considerations of hydrophobic interactions, then the negative parameters observed for glucagon association can be readily understood. The hydrophobic interaction is therefore not necessarily controlled by the entropy change because, if there are significant conformational changes, the reaction may be controlled by the enthalpy change. Consequently, the more important parameter characteristic of all hydrophobic reactions is the heat capacity change.


Evidence against phospholipid asymmetry in intracellular membranes from liver. We have studied the distribution of phospholipids across the membrane of microsomal vesicles and Golgi-derived secretory vesicles from rat liver by the use of phospholipases. Model studies on single-bilayer phospholipid vesicles showed that phospholipase A2 (phosphatide 2-acyl-hydrolase, EC 3.1.1.4) cleaved at least 80% of the lipids on the outer surface of such vesicles without significant attack on the inner surface. In microsomal vesicles approximately 40% of the outer surface phospholipids were cleaved before the enzyme gained access to the interior of the vesicles. The same conclusion was reached for Golgi vesicles. By following the degradation of the three major phospholipids in intact microsomes and in extracted lipids we found that the same fraction of each of these phospholipids was exposed on the outer surface of the microsomal vesicles. Corresponding experiments with Golgi vesicles showed that distinctly different fractions of phosphatidylcholine and phosphatidylethanolamine were present on the surface of these vesicles. However, the difference was accounted for by enrichment of phosphatidylcholine in intravesicular particles rather than by asymmetry across the vesicle membrane. The results from specific hydrolysis of phosphatidylinositol confirmed an essentially symmetric distribution of this phospholipid across the microsomal and the Golgi vesicle membranes.


Opiate-dependent modulation of adenylate cyclase. Reactions mediated by the opiate receptors that inhibit adenylate cyclase (EC 4.6.1.1) are closely coupled to subsequent reactions that gradually increase adenylate cyclase activity of neuroblastoma X glioma NG108-15 hybrid cells. Opiate-treated cells have higher basal-, prostaglandin E1-, and 2-chloroadenosine-stimulated activities than do control cells. However, NaF or guanosine 5'-(beta, gamma-imido)triphosphate abolishes most of the differences in adenylate cyclase activity observed with homogenates from control and opiate-treated cells. Cycloheximide blocked some, but not all, of the opiate-dependent increase in adenylate cyclase activity. These results suggest that the opiate-dependent increase in adenylate cyclase is due to conversion of adenylate cyclase to a form with altered activity. Protein synthesis also is required for part of the opiate effect. We propose that activity of adenylate cyclase determines the rate of conversion of the enzyme from one form to the other and that opiates, by inhibiting adenylate cyclase, alter the relative abundance of low- and high-activity forms of the enzyme.


Microtubule structure at low resolution by x-ray diffraction. Analysis of x-ray diagrams of oriented hydrated cytoplasmic microtubules shows that the tubule wall extends from about 70 to 150 A radially. The central region of the wall appears homogeneous, but the outside surface is subdivided by vertical grooves separating the 13 protofilaments and by a steep 10-fold family of grooves. The inside surface is dominated by the 10-start grooves with no clear subdivision between the protofilaments.


Tripartite model for the photochemical apparatus of green plant photosynthesis. Equations for fluorescence and the rates of photochemistry of photosystem I and photosystem II are derived from a photochemical model for the photosynthetic apparatus that includes the various interactions of the light-harvesting chlorophyll a/b complex with photosystem I and photosystem II as specific photochemical rate constants. The degree of coupling between photosystem II and the chlorophyll a/b complex which is expressed as a product of two probability terms plays a central role in this three-pigment system. The cycling of excitation energy back and forth between photosystem II and the chlorophyll a/b complex increases the exciton density in both arrays of chlorophyll according to a simple analytical expression in the equations. These equations of the tripartite model provide new and credible insights into the photochemical apparatus of photosynthesis.


Enucleation and reconstruction of interferon-producing cells. Enucleation of L cells leads to loss of the capacity to produce interferon, showing that the cell nucleus is essential for interferon formation. However, when the cells were enucleated while interferon formation. However, when the cells were enucleated while interferon formation was proceeding, the cytoplasts were capable of continuing to synthesize interferon by a process shown to be protein synthesis, showing that the interferon messenger RNA leaves the nucleus after synthesis. Reconstructed cells were obtained by Sendai virus fusion of karyoplasts and cytoplasts. Such reconstructed cells were capable of producing at least as much interferon (43 interferon units/10(4) nucleated cells) as control cells (31 interferon units/10(4) nucleated cells).


Interferon messenger RNA content of human fibroblasts during induction, shutoff, and superinduction of interferon production. Translation of injected mRNA in oocytes of Xenopus laevis has been used as a highly sensitive and quantitative assay for interferon mRNA. Injection into oocytes of polyadenylylated RNA extracted from poly(I).poly(C)-induced human diploid fibroblasts (FS-4) leads to the synthesis of biologically active human fibroblast interferon over a period of 24-32 hr. There is a linear relationship between the amount of mRNA injected and the interferon yield obtained over a range of 1-20 ng of injected RNA. Injection of 40-80 ng of mRNA into each of 15 oocytes, homogenized in 0.3 ml of incubation medium, gave a titer of 128-256 interferon reference units/ml of homogenate.FS-4 cells at the peak of interferon production-i.e., approximately 2.5 hr after the beginning of induction with poly(I).poly(C)-gave mRNA that yielded 24-48 interferon reference units/ml in the oocyte assay (30 ng of RNA injected per oocyte). An equivalent amount of mRNA from FS-4 cells in the shutoff phase, approximately 6 hr after induction, gave </=4 interferon reference units/ml. In contrast, mRNA extracted from FS-4 cells that had been induced and maintained in the presence of 40 muM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole for 6 hr produced 64-128 interferon reference units/ml. Polyadenylylated RNA obtained from uninduced FS-4 cells did not lead to detectable interferon synthesis (<4 interferon reference units/ml). These data provide a direct verification of the hypothesis that the shutoff of interferon production in FS-4 cells involves a regulatory event leading to the posttranscriptional inactivation or degradation of interferon mRNA. Because the inactivating mechanism is sensitive to inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, a selective inhibitor of nuclear heterogeneous RNA and mRNA synthesis, it is likely that synthesis of an RNA molecule is necessary for the shutoff of interferon production.


Vasoactive intestinal polypeptide in brain: localization in and release from isolated nerve terminals. The vasoactive intestinal polypeptide was present in synaptosomal (nerve ending) preparations from cerebral cortex, hypothalamus, and striatum of rat brain in higher concentrations than in these tissues as a whole. The total content and relative specific activity of the peptide increased with progressive purification of the synaptosomal fractions and generally followed the distribution of known synaptosomal constituents--dopamine, norepinephrine, and lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27). The peptide was also released from synaptosomal pellets with increased K+ concentration, and this release was Ca2+-dependent. The findings suggest a role for vasoactive intestinal polypeptide as a transmitter or modulator of synaptic function.


Fibroblast heterogeneity and prostaglandin regulation of subpopulations. The effects of prostaglandin E(2) (PGE(2)) upon the synthesis of protein and DNA, and membrane transport of proline and thymidine, by human diploid fibroblasts were studied. At a concentration range of 1-10 muM, PGE(2) inhibited protein synthesis and membrane transport by 45-50%. Serum-activated DNA synthesis and thymidine transport were also inhibited by approximately 50% in cells made quiescent and synchronous by serum deprivation. To determine whether prostaglandin inhibits some of the cells completely or all of the cells partially, radioautographic and cell-counting experiments were done. In cultures pulse-labeled with [(3)H]thymidine 12-33 hr after serum activation, prostaglandin exposure reduced the number of labeled nuclei by 42%. Sixty-five hours after serum activation, the total cell numbers present in the PGE(2)-exposed cultures were reduced by 25%. Furthermore, in the fibroblast cultures derived from cells previously maintained in 10 muM PGE(2) for 14 days, PGE(2) had no effect on DNA synthesis, indicating that the PGE(2)-sensitive cells had disappeared from the cultures. Thus, PGE(2) appears to inhibit growth and synthesis of a subpopulation of cells while not affecting the remaining insensitive cells. Prostaglandins may play an important role in connective-tissue differentiation and in some pathologic alterations by regulating fibroblast subpopulations.


Random assembly of different kinds of small subunit polypeptides during formation of fraction I protein macromolecules. Maternal inheritance determine the charge on the large subunit of fraction I protein whereas both parents of an interspecific F(1) hybrid plant make an equal contribution to the charge of the small subunit. Experiments were performed to test whether fraction I protein in the hybrid plant was a hybrid molecule or two kinds of protein molecules, one composed of large subunits combined with small subunits of the male type and the other composed of large subunits combined with small subunits of the female type. A mixture of fraction I proteins from Nicotiana langsdorffii and N. bonariensis was resolved into two components of different charge by agarose gel electrophoresis but the protein from the F(1) hybrid plant between the two species was a single component. However, two-dimensional agarose gel electrophoresis showed that fraction I protein from an F(1) hybrid could be highly heterogeneous in charge compared to a fraction I protein containing a single small subunit polypeptide that was homogeneous in charge. Evidently, charge heterogeneity results from random self-assembly of the small subunit polypeptides. Random self-assembly of small subunits of two types could result in a mixture in which 99.2% of the population are hybrid molecules composed of seven types together with 0.39% containing small subunits of the maternal type and 0.39% containing those of the paternal type. In an F(1) hybrid plant in which three small subunit polypeptides randomize during assembly, a mixture of 45 types of fraction I protein macromolecules could be present.


Tumor promoters inhibit spontaneous and induced differentiation of murine erythroleukemia cells in culture. Addition of the potent tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), to murine erythroleukemia cell lines in suspension cultures inhibited both spontaneous differentiation and differentiation induced by hexamethylene bisacetamide (HMBA), dimethyl sulfoxide, or butyric acid. Inhibition was unrelated to cytotoxicity and was reversible. When several plant diterpenes were tested, there was a positive correlation between tumor-promoting activity and inhibition of differentiation. TPA inhibited HMBA-induced differentiation only if added prior to the time of commitment to differentiation, as assayed by scoring for differentiation after transfer of cells from HMBA to fresh medium without HMBA. TPA-mediated inhibition of differentiation was associated with a decrease in globin mRNA accumulation.


Flagellar mutants of Chlamydomonas: studies of radial spoke-defective strains by dikaryon and revertant analysis. The motility mutant of Chlamydomonas reinhardtii pf14 lacks radial spoke structures in its flagellar axonemes, and 12 proteins present in wild type are missing from a two-dimensional map (isoelectrofocusing/sodium dodecyl sulfate electrophoresis) of its (35)S-labeled flagellar proteins. Six of these same proteins are missing in pf1, which lacks spoke-heads. To determine whether any of the missing proteins represent the mutant gene product two experimental approaches have been applied. The first makes use of the fact that gametes of either mutant strain when fused with wild-type gametes to form quadriflagellate dikaryons undergo recovery of flagellar function. Recovery at the molecular level was monitored by prelabeling the mutant proteins with (35)S and allowing recovery to occur in the absence of protein synthesis. It is to be expected that the mutant gene product would not be restored as a radioactive protein and that recovery would depend on the assembly of the wild-type counterpart that is not labeled. The second technique makes use of revertants induced by UV irradiation. Dikaryon rescue in the case of pf14 leads to restoration of 11 radioactive components; only protein 3 fails to appear as a radioactive spot. For pf1 only two radioactive proteins are restored; proteins 4, 6, 9, and 10 were not radioactive. Analysis of revertants of pf1 gave evidence (altered map positions) that protein 4 is the mutant gene product. In the case of pf14, analysis of 22 revertants has not provided similar positive evidence that protein 3 is the gene product.


Addition of colchicine--tubulin complex to microtubule ends: the mechanism of substoichiometric colchicine poisoning. Colchicine blocks microtubule polymerization by an unusual substoichiometric poisoning mechanism. We have investigated the mechanism by which this poisoning occurs with several experimental approaches, and have found that colchicine acts by addition to microtubule ends as a colchicine-tubulin complex.


Parental investment, mate choice, and mate quality. Current theory in sexual selection is extended to predict within-sex variability with regard to selectivity towards mates in different mating systems. Generally, the sex that invests more in the care of each offspring should be more selective of mates than the sex investing less. Within each sex, individuals of low male quality should be less selective than individuals of high quality, but there should be less variation in selectivity among individuals of the sex investing more. When only one sex contributes parental care, however, individuals of that sex should be uniformly selective, while the other sex is expected to mate indiscriminately. Using feral pigeons (Columba livia), these hypotheses are tested for the case in which both sexes contribute substantial parental care, but in which females contribute more than males. As predicted, females were found to be more selective of mates than males were. On certain criteria, males of lower quality were less selective of mates than males of higher quality.


Transfer of codominant markers by isolated metaphase chromosomes in Chinese hamster ovary cells. Codominant mutations to methotrexate and ouabain resistance in Chinese hamster ovary cells can be transferred to recipient Chinese hamster ovary cells by isolated metaphase chromosomes. For methotrexate, both the structural change and the increased activity of dihydrofolate reductase (5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase EC 1.5.1.3), characteristic of the donor cells, are observed in the transferents (cells that carry and express functions derived by chromosome transfer). The transferents are unstable in the absence of selection although stable clones can be isolated. From results obtained by fractionation of chromosomes and transfer to recipients, the methotrexate and ouabain markers can be assigned to the middle and large size-classes of chromosomes, respectively. By fractionation and transfer of chromosomes, from transferents to new recipients, evidence has been obtained that chromosome integration is not restricted to a particular chromosomal site in the recipient.


Theories of quasi-linkage and "affinity": some implications for population structure. "Quasi-linkage" refers to nonrandom assortment of genes located on different chromosomes. Although this phenomenon has been widely observed in many organisms since the early part of this century, it is barely known. Interest in it was recently rekindled by the report of an association between quasi-linkage and the expression of genes belonging to a group of cancer viruses whose genomes are integrated in mouse chromosomes. This prompted an examination of the question whether "sustained meiotic affinity," which is one of the explanations proposed for quasi-linkage, can influence population structure in a manner unattainable by other known modes of heredity. It is shown for a two-locus two-allele system that equilibrium is attained with the gametic phase disequilibrium D greater than 0, leading to a permanent excess of the preferred genotypes. The possible relationship of these concepts to the inheritance of susceptibility to cancer and other diseases is discussed.


Mutation frequencies in female mice and the estimation of genetic hazards of radiation in women. The female germ cell stage of primary importance in radiation genetic hazards is the immature, arrested oocyte. In the mouse, this stage has a near zero or zero sensitivity to mutation induction by radiation. However, the application of these mouse results to women has been questioned on the ground that the mouse arrested oocytes are highly sensitive to killing by radiation, while the human cells are not; and, furthermore, that the mature and maturing oocytes in the mouse, which are resistant to killing, are sensitive to mutation induction. The present results have a 2-fold bearing on this problem. First, a more detailed analysis of oocyte-stage sensitivity to killing and mutation induction shows that there is no consistent correlation, either negative or positive, between the two. This indicates that the sensitivity to cell killing of the mouse immature oocyte may not be sufficient reason to prevent its use in predicting the mutational response of the human immature oocyte. Second, if the much more cautious assumption is made that the human arrested oocyte might be as mutationally sensitive as the most sensitive of all oocyte stages in the mouse, namely the maturing and mature ones, then the present data on the duration of these stages permit more accurate estimates than were heretofore possible on the mutational response of these stages to chronic irradiation.


Hybridization properties of immunoglobulin mRNA: failure to detect covalently associated IgG mRNA transcripts of reiterated and unique mouse DNA. Messenger RNAs for antibody heavy (gamma) and light (kappa) chains were isolated from the polysomes of an IgG-producing mouse myeloma cell line. Polysomes engaged in heavy or light chain synthesis were separated by immunoprecipitation using rabbit antibodies specific for the mouse IgG formed. The mRNAs obtained, more than 85% specifying IgG [Legler, M. & Cohen, E. P. (1976) Biochemistry 15, 4390-4399], were used as "probes" in hybridization experiments with sheared mouse liver DNA. To determine whether mRNAs for Ig heavy and light chains contained covalently bound transcripts of unique and reiterated DNA, hybrids were isolated with or without treatment with ribonuclease (RNase) prior to fractionation and the apparent rates of hybridization were compared. A monophasic C(o)t (DNA concentration x incubation time) curve with a C(0)t(1/2) of 4000 moles of nucleotide per liter x sec, corresponding to less than five hybridization sites per haploid genome, was obtained whether or not RNase was used in the isolation protocol. With a similar experimental design, the apparent hybridization rates of heterogeneous nuclear RNA from the same cell source were clearly different. The "stringency" of the reaction was reduced by incubating the hybridization mixtures at lower temperatures in a further attempt to detect a large class of repetitive sequences that would form hybrids with the IgG mRNA used, if such sequences were present. The results, however, were the same; i.e., the apparent rates of hybridization of mRNAs for mouse antibody gamma and kappa chains with sheared mouse liver DNA were essentially the same whether or not RNase was used in the isolation procedure. Reiteration of genes in mouse liver DNA for mouse IgG could not be detected.


Zinc-binding ligands in milk and intestine: a role in neonatal nutrition? The hypothesis that a zinc-binding ligand (ZBL) recently discovered in human milk but absent from cow's milk might be related to zinc nutrition in the neonate was investigated. The zinc-binding characteristics of rat milk were examined to determine if the rat was a suitable model. By gel filtration, rat milk was found to contain a ZBL with characteristics similar to those of the ZBL found in human milk. A similar ZBL was identified in the intestinal mucosa of rats 16 days of age and older but was absent in rats from birth to 16 days. These results support the hypothesis that the ZBL of maternal milk may enhance zinc transport in the neonatal period before the development of intestinal mechanisms for zinc absorption.


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 semi-synthetic diet enriched in sucrose. Lean littermates do not develop fatty livers 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.


Enzyme replacement therapy in Gaucher's disease: large-scale purification of glucocerebrosidase suitable for human administration. Enzyme replacement therapy for the alleviation of Gaucher's disease has been impeded because of the difficulty in preparing large amounts of glucocerebrosidase, the enzyme that is deficient in patients with this disorder. A large-scale procedure for the purification of human placental glucocerebrosidase has been developed. The method uses cholate extraction, ammonium sulfate fractionation, acid precipitation, butanol extraction, and hydrophobic chromatography; the final enzyme preparation has a specific activity of more than 10(6) units/mg of protein with an overall recovery of 30%. In addition, the contamination of enzyme preparations, intended for human infusion, prepared by isolation procedures involving concanavalin A columns has been studied and is reported here.


Localization of motor neuron pools supplying identified muscles in normal and supernumerary legs of chick embryo. Neuromuscular specificity has been investigated in chick embryos with a grafted supernumerary leg. The nerves of the lumbar plexus are divided between the two legs so that rostral nerves innervate the grafted leg and the caudal nerves supply the host's original leg. The basic topographic organization of the histologically definable motor neuron clusters of the lateral motor columns remains unchanged by the addition of a supernumerary leg. Intramuscular injections of identified leg muscles have been used to map the intraspinal location of specific motor pools in stage 38 (12-day) embryos. In the normal embryo, the gastrocnemius muscle is innervated by neurons in a central dorsal cluster of motor neurons in segments 26-29. In six experimental cases, the motor neurons supplying the gastrocnemius muscle of a rostrally placed grafted leg were consistently located in a specific medial cluster of neurons in segments 23-25. Motor neurons in this location never normally innervate a gastrocnemius muscle, even in the very young embryos during the period of naturally occurring cell death. This observation of a systematic mismatch between a particular motor cluster and an abnormally innervated muscle indicates the operation of a selective developmental process. A hierarchy of selective chemoaffinities may best explain our experimental results.


Conformational requirements for dopamine-induced vasodilation. The availability of a series of semi-rigid analogs of dopamine and epinine has made it possible to investigate the conformational requirements for action on dopamine and beta2-adrenergic vascular receptors. The analogs were screened for dopamine-agonist action by intra-arterial injections into the renal vascular bed and for beta2-adrenergic activity by similar injections into the femoral vascular bed in dogs pretreated with phenoxybenzamine. 2-Amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-6,7-DTN) and its N-methyl derivative (analogous to the trans beta rotamer of dopamine) exhibited pronounced dopamine-agonist activity and minimal beta2-adrenergic activity. In contrast, the semi-rigid analog of the trans alpha rotamer of dopamine (2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene; A-5,6-DTN) and its N-methyl derivative exerted pronounced beta2-adrenergic activity but were inactive as dopamine agonists.6,7-Dihydroxytetrahydroisoquinoline, a semi-rigid analog of the cis beta rotamer of dopamine, did not produce renal vasodilation. These results indicate that a conformation of dopamine similar to that found in A-6,7-DTN is required for dopamine-vascular activity, while the conformation found in A-5,6-DTN is preferred for interaction with beta2-adrenergic receptors.


Abnormal lithium and sodium transport in erythrocytes of a manic patient and some members of his family. This paper compares the transport of Li(+) and Na(+) in erythrocytes from a patient with mania and from members of his family to that in erythrocytes from normal humans. In normal human erythrocytes, Li(+) is transported by at least three operationally distinct pathways: one inhibited by ouabain (ouabain-sensitive), one by phloretin (phloretin-sensitive), and one not inhibited by either compound (insensitive). Li(+) can be driven up its electrochemical potential gradient by an oppositely directed electrochemical potential gradient for Na(+)-i.e., Li(+)/Na(+) counterflow can occur-through the phloretin-sensitive pathway but not through the other two pathways. Because ouabain-sensitive Li(+) transport is negligible under physiological conditions, Li(+) distribution between erythrocytes and plasma in vivo depends mainly on the balance between Li(+)/Na(+) counterflow and the insensitive pathway(s) of Li(+) transport. The steady-state ratio of Li(+) concentration in the erythrocytes to that in the plasma of the patient was between 2 and 3 times higher than the comparable ratio in normal persons. The phloretin-sensitive Li(+)/Na(+) counterflow system was almost absent in the erythrocytes of the patient. Furthermore, unlike those from normal individuals, the patient's erythrocytes showed no external Li(+)-stimulated, phloretin-sensitive, ouabain-insensitive Na(+) efflux. The magnitudes of the ouabain-sensitive and insensitive pathways for Li(+) transport in the patient's erythrocytes were within normal limits. The decreased Li(+)/Na(+) counterflow in the patient's erythrocytes was probably not due to the presence of an inhibitor in the plasma of the patient but rather to an intrinsic defect in the erythrocytes. Because the father and several siblings of the patient showed a similar abnormality in erythrocyte Li(+)/Na(+) transport, it is probable that this defect is inherited.


Calcium translocation by Golgi and lateral-basal membrane vesicles from rat intestine: decrease in vitamin D-deficient rats. Intestinal Ca2+ transport was studied in membrane vesicles isolated from microvillus, Golgi, and lateral-basal membrane preparations. Ca2+ uptake by these vesicles was measured by determination of 45Ca2+ associated with these membranes after collection by micropore filtration. Golgi membranes showed the highest initial rate and equilibration level of Ca2+ uptake. Approximately 90% of this Ca2+ uptake was into an osmotically responsive space, suggesting that what was measured was predominantly Ca2+ translocation. Vitamin D-deficient rats showed a markedly diminished rate of uptake and level of equilibration. These data indicate that a Ca2+-translocating process was associated with Golgi membranes to a greater extent than with surface membranes and that this process was markedly decreased in vitamin D-deficient rats. The results suggest that the Golgi apparatus participates in intestinal Ca2+ absorption.


Theoretical study of the effect of enzyme-enzyme interactions on steady-state enzyme kinetics. Equilibrium statistical mechanics is much concerned with problems involving intermolecularinteractions, either in lattices or in pure fluids or solutions. The possibility of enzyme-enzyme interactions suggests that the same problems might be studied profitably at steady state as well as at equilibrium. In the systems we consider, each of the identical enzyme molecules of the system undergoes steady-state stochastic cycling among states i equal 1,....,n. But the molecules do not cycle independently. Two neghboring molecules, in states i and j, interact with a free energy wij (a function of the distance r in the solution case). The instantaneous transition probabilities between states for a given molecule will depend on the instantaneous interactions between the molecule in question and its neighbors. The primary question of interest is how the enzyme flux is influenced by the interactions. The general problem is outlined here and some simple special cases are treated. The discussion will be continued in a following paper [Hill, T. L. (1977) Proc. Natl. Acad. Sci. USA 74, in press]