Reflective and impulsive children: strategies of information processing underlying differences in problem solving. The hypothesis that impulsive children differ from reflective children in their preferred strategy of information processing, based on extent of stimulus analysis, was investigated. The experiments employed different age groups and a variety of tasks, including matching, grouping, recall, and concept attainment. Stimuli were presented both visually and auditorily and included both visually and aduitorily and included both verbal and pictorial matrials. The tasks required verbal and nonverbal responses and varied in the level of stimulus analysis necessary for successful performance. The subjects' strategy was assessed by the quality of their performance on tasks requiring detail versus global processing, and by the strategy they chose to adopt in tasks where either detail or global processing led to successful performance. While reflective children performed better on tasks requiring detail analysis than on tasks requiring global analysis, impulsive children showed the reverse trend. Furthermore, when successful solutions could be reached via either a global- or a detail-processing strategy, impulsive children who adopted the former were equally as successful as reflective children who adopted the latter strategy. It was concluded that, contrary to existing views, impulsive children are not inferior to reflective children in general potential or problem-solving ability. Rather, the inferior performance of impulsive children frequently reported in the literature may be due to incompatibility between their preferred global-processing strategy and the detail analysis typically required for successful performance.


Spontaneous regression of hematologic cancers. Spontaneous regression of hematologic cancer is extremely rare. Data gleaned from the literature and from previously unreported cases allow certain interesting general conclusions. Spontaneous remission of acute leukemia is associated with bacterial infection and is of short duration, weeks to months. Spontaneous regression of lymphoma or plasma cell dyscrasia is often of substantial duration, months or years, and frequently is associated with viral infections. Spontaneous regression of chronic lymphocytic leukemia is also of significant duration and has been associated with the occurence of a new primary carcinoma in one-third of the cases.


Spontaneous regression of neuroblastoma. Case of spontaneous regression of neuroblastoma continue to occur in the present multimodal therapy era at institutions where physicians are prepared to withhold treatment on certain patients with residual primary or metastatic disease. From a survey of the 22 member institutions of Children's Cancer Study Group, seven hospitals submitted data on 24 neuroblastoma patients whose disease underwent regression after minimal, unusual, or no treatment. An analysis of these patients and of 33 patients form two large series in the literature shows that the majority of patients are infants with Stage II or Stage IVS disease. The spontaneous regression usually consists of complete disappearance of the disease, but in some neuroblastomas, maturation to ganglioneuroma takes place. The various factors that may influence regression are discussed.


Latent carcinoma and carcinoma in situ.

Latent carcinoma and carcinoma in situ. Lesions exist in the cervix that are diagnosed as carcinoma in situ; some may progress to invasive carcinoma and some may regress. Many are probably overdiagnosed, may represent effects of promoting agents rather than intiating agents, and may entail risk for the patient in that the lesion may be an unusualy good target in carcinogenesis. Latent carcinomas are small foci of initated cells unable to express their malignant phenotype because of environmental controls. Latent cells are produced in experimental carcinogenesis and occur in spontaneous tumors as G-O stem cells.


Effects of estrogen on the electrical activity of identified and unidentified hypothalamic units. Experiments performed on unanesthetized ovariectomized female rabbits demonstrated the effects of estradiol benzoate (EB; 20 microng i.v.) on the electrical activity of hypothalamic units which send their axons to the median eminence. Of a total of 1,840 cells recorded in hypothalamic and preoptic areas, 46 (2.5%) were antidromically activated by stimulating the median eminence. Under the present experimental conditions, EB induced a progressive diminution in the mean firing rate of these cells observed throughout the recording period (30-120 min). In addition to cells projecting to the median eminence, neurons which could not be antidromically invaded using our techniques were observed to be sensitive to estrogen. Estrogen administration produced a long-lasting inhibition of antidromically activated cells and a depression of much shorter duration (15-20 min) of unidentified nonstimulated units. These data suggest the existence of two types of hypothalamic neurons sensitive to estrogen.


Neuroendocrine and electroencephalographic sleep changes due to acute amphetamine ingestion in human beings. Amphetamine, a clinically used sympathomimetic central-acting drug, was administered in Spansule capsules in a blind schedule to 8 normal obse volunteers in a daily (8 a.m.) single 15 dose for 7 days. The study, conducted in the metabolic ward, included two 7 day placebo periods (pre- and post-drug). During the 1st placebo period, all subjects exhibited within the 1st 2 h of sleep a clear and significant nocturnal increase of growth hormone (GH) closely related with sleep stages 3 and 4. Thyrotropin (TSH) increase was observed between 01.00 to 04.00 h and was accompanied by a reduction of thyroxine (T4) levels. Cortisol levels presented their characteristic rhythm, clearly associated with paradoxical sleep (REM). Amphetamine significantly reduced stages 3 and 4, as well as REM sleep, and increased stage 2. GH and cortisol circadian profiles were preserved, although their magnitude was diminished. The extent of nocturnal TSH and T4 changes was significantly reduced. Drug withdrawal was accompanied by a rebound of REM sleep and a trend to recover the pretreatment TSH and T4 temporal profile. These results suggest that adrenergic neurotrasmitters may be a significant modulating system for TSH and cortisol, whereas GH nocturnal secretion may be influenced by different mechanisms.


Growth hormone and prolactin in the fetus. Growth hormone is released from pituitary glands maintained in tissue culture as early as 5 weeks after conception. It has been identified in the fetal anterior pituitary gland by immunologic and biologic techniques between 7 and 15 weeks of gestation. Immunoreactive pituitary GH levels increase rapidly between 10 and 14 weeks of gestation to maximal levels at 30-34 weeks. Serum GH levels are detectable by 10-weeks postconception and reach maximal values at 20-24 weeks declining thereafter until term. Pospartum GH concentrations decline over several weeks to lower values, GH levels remaining higher in preterm than in term infants. The biologic role of pituitary GH in the fetus is unknown. Although birth-weights and lengths are reported to be normal in infants with anencephaly, aplasia, or hypoplasia of the pituitary gland and in isolated deficiency of growth hormone, in whom pituitary and serum GH levels are low, careful inspection of large series of such infants reveals that their birthweights may indeed be low and that cell numbers in many organs may be subnormal. In experimental animals prenatal administration of GH increases maternal weight and gestational length. Reported effects on neuronal growth and adult intelligence of animals treated prenatally may reflect these phenomena rather than a direct transplacental effect of GH. Prolactin is also elaborated by the pituitary gland of very young human fetuses. It has been identified immunologically by 10-weeks gestation and biologically at 18 weeks. Pituitary content of immunoreactive prolactin remains low until 16.5-weeks gestation and then increases steadily until term. The plasma concentration of prolactin is low until 30-weeks gestation and increases thereafter until term. In anencephalic fetuses prolactin levels are normal and respond to appropriate stimuli. Very high concentrations of (possibly fetal) prolactin are found in the amniotic fluid. The role of prolactin in the fetus is also unknown. It has been suggested that prolactin may be important for growth of the fetal adrenal cortex and/or for suppression of the immune response during pregnancy. It is apparent that a great deal of additional work is necessary before the importance of either growth hormone of prolactin for normal fetal growth and development will be known.


Blood pressure, edema and proteinuria in pregnancy. 4. Blood pressure relationships. The significance of these and related data will be discussed in greater detail during the subsequent course of this workshop. For now, we can sum up our findings with the following general statements concerning this analysis: 1. Blood pressure elevation occuring alone during the course of pregnancy, in the absence of edema and/or proteinuria, affects perinatal survival adversely. 2. This relationship is most marked among nulliparas in the age range 20-34 years and is less pronounced, but still evident, in young nulliparas and in multiparas of comparable age. 3. The effect is greater among black patients than among white patients in the median-aged nulliparas and multiparas, but this difference is not mirrored in the young nulliparas studied. 4. Blood pressure elevations during weeks 20-28 of pregnancy result in much higher subsequent perinatal losses in white nulliparas (both median and young age groups) than comparable elevations earlier or later in pregnancy. 5. Among black nulliparas of median age, maximal blood pressure effect on outcome is encountered at the sixteenth week (the earliest available data), with continuing significant increases until the twenty-eighth week, and there is another increment at term. In younger black patients, the results from 20 through 28 weeks parallel those seen in white patients, but with an additional peak at term. 6. among multiparas, maximal effect occurs at 24-28 weeks in both black and white groups. 7. The critical blood pressure levels are significantly lower in early pregnancy than in late pregnancy. 8. Critical levels of blood pressure with advancing pregnancy appear to parallel the trend in mean blood pressures determined to exist for this series. 9. Utilizing blood pressure distribution data to set limits statistically, we find very meaningful increments in perinatal mortality rates for nulliparas presenting blood pressure elevations beyond the 95 percentile point. This holds also for diastolic or systolic levels when these are examined independently because neither alone yielded more convincing data than blood pressure combinations condidered together.


Blood pressure, edema and proteinuria in pregnancy. 6. Proteinuria relationships. 1. The blood pressures of pregnant patients with proteinuria seem to be no higher than the levels of blood pressure in patients with no proteinuria. The presence of proteinuria and pregnancy in the absence of blood pressure elevation increases perinatal mortality above the values where blood pressure elevation occurs alone. This relationship is most prominent among nulliparous median-age pregnant patients. Even though the number of patients is small, the highest rates occur in the young white nullipara from the sixteenth to twenty-third week of pregnancy. Attempts to compare black and white median-aged nulliparas are meaningless because of the tremendous variability of data. 2. The findings in all cohorts with proteinuria were essentially the same as those in Cohorts I, II and III. Proteinuria of 2+ or greater occurs more frequently in black than in white gravidas. 3. Our observations indicate that perinatal mortality rates in patients with proteinuria are, for the most part, at least twice the rates of patients without proteinuria. 4. The volume of data available is insufficient to determine whether proteinuria influences prematurity rates or mean birth weights. However, our data suggest that some vascular or renal lesion must be affecting perinatal mortality. 5. The small number of patients in the proteinuria study group does not permit meaningful comparisons with the patient group presenting no edema or proteinuria. 6. Adherence to suitable criteria for discovering and measuring proteinuria is necessary to make the diagnosis of preeclampsia. These criteria include careful collection of urine in the clinic or hospital, utilization of acceptable standard testing methods, and the application of uniform principles of medical practice to the overall care of obstetric patients. 7. The data are presented, not interpreted. However, we cannot discount the value of the present data in suggesting the urgent need to restudy more of the current data available. It also seems desirable to initiate another program to investigate a smaller group of patients made up of the same sequential cohorts where it may be possible and more practical to apply strict supervision of statistical design, patient care, personnel, laboratory testing, data recording, data processing and reporting and statistical analysis.


Blood pressure, edema and proteinuria in pregnancy. 7. Edema-plus-proteinuria relationships. 1. A total of 488 pregnancies had the combination of two-plus or more proteinuria and edema of the hands and face. Of these, 208 were white and 280 were black gravidas. In the white gravidas, 8 fetal and neonatal deaths occurred with a perinatal mortality of 38.5 per 1,000. There were 13 perinatal deaths in the black subgroup with a perinatal mortality rate of 46.4 per 1,000. The overall perinatal mortality rate was 43.0 per 1,000, which could be compared to the overall perinatal mortality rate of 32.8 per 1,000 for the segment of the study population without edema or proteinuria. This underscored the implication of increased hazard to fetal outcome of these clinical signs in combination. 2. The analysis of the matrix data showed scattered rates throughout gestation in white median-age nulliparas. Their black counterparts had comparable increased mortality rates. In the white multiparas of ages 20 to 34 years, the highest rates were found at relatively low blood pressure levels. The black median-age multiparas had rates associated with higher pressure readings, especially at or above 125/75. In teenage mulliparas with edema and proteinuria, perinatal mortality rates were similar for both subgroups and were found in somewhat lower blood pressures. 3. The incremental analysis was remarkable in that rates were scattered widely in the white subgroups, but tightly clustered in the black subgroups. The black median-age nulliparas had perinatal mortality concentrated about 115 to 134 mm. Hg systolic and 65 to 84 mm. Hg diastolic. The overall mortality rates of this subgroup were the highest of the subgroups studied. The black 20 to 34 year old multiparas had highest coassociated deaths in the 134-154 mm. Hg systolic levels throughout pregnancy. The clustering effect was most pronounced in black teenage nulliparas in both systolic and diastolic blood pressure groups at much lower levels. 4. The use of a critical cut-off blood pressure level of 125 mm. Hg systolic and 75 mm. Hg diastolic emphasized the combination factor effect, especially by the increased perinatal mortality rates in the black median-age subgroups of both nulliparas and multiparas. In the white median-age subgroups the rates were not uniformly affected. The teenage nulliparas as a group showed increased mortality rates with lower pressure levels in general. This was seen when the diastolic level was above 75 mm. Hg. 5. Perinatal mortality rates of nulliparas were increased by proteinuria and edema. This increase was great in the case of the 20 to 34 year old black nulliparas, particularly in association with increased blood pressure. Trends are not so apparent for the white median-age nulliparas. Nulliparas of 19 years of age or less have higher perinatal loss with edema and proteinuria, but this is not necessarily augmented with blood pressure elevation. This is notably so in teenage black nulliparas in the early periods of gestation and at term.


Blood pressure, edema and proteinuria in pregnancy. 8. Evaluation of criteria. We have reviewed some of the potential sources of errors in our study data with regard to the criteria used clinically to diagnose toxemia. The constraints imposed are rather clear. Despite these limitations (or perhaps because of them), we are impressed that the trends noted in the foregoing studies reported in this workshop relating to gestational progression and perinatal outcome have been encountered. Because such relationships have been uncovered using relatively coarse study parameters, we are tempted to infer that they are likely to be correct. If indeed such trends were spurious or weak relationships, the indelicate clinical signs at our disposal (in terms of their reliability and reproducibility) should not have been expected to demonstrate them so cogently. At the same time it should be made clear that more subtle correlations may exist, other than those herein shown, which perforce cannot be demonstrated or proved because of the restrictive unreliability of the clinical observations.


Blood pressure, edema and proteinuria in pregnancy. 9. Proposal for classification. The frequency distributions of blood pressures in large populations fail to show two groups, one normotensive and the other hypertensive. In the spectrum of pressures, some people merely have higher levels than others and division of abnormal from normal is artificial and arbitrary, although it is useful for prognosis. The blood pressure of 140/90 as the conventional dividing line does not seem to be appropriate in pregnant women. From the standpoint of fetal prognosis, a level of 125/75 before the thirty-second week and 125/85 thereafter seems more reasonable. Moreover, those levels are close to the 120/80 that Robinson and Brucer specified as the upper limit of normal for all adults and are close to the 130/70 and 120/80 that the eminent British authority, F.J. Browne, used successively in the diagnosis of hypertensive disorders in pregnancy. If the standard of 125/75 were adopted, however, a quarter of all pregnant women would be hypertensive in the second trimester and half in the last month, which are disturbingly high proportions. For the diagnosis of preeclampsia, a rise in blood pressure probably is more significant than an arbitrary level. The usual blood pressure in midpregnancy merely defines the patient's place in the spectrum. Figure 9-1 indicates that in white nulliparas the diastolic pressure rises an average of 10 mm. Hg in the middle of the third trimester. If the mean and median are close together, greater increases would occur in half of the women. The classification of the American Committee on Maternal Welfare and of the Committee on Terminology of the American College of Obstetricians and Gynecologists specify increases of 30 mm. Hg or more in the systolic or 15 mm. Hg or more in the diastolic pressures as criteria of preeclamptic hypertension. pperhaps the rise in diastolic pressure should be set at some greater value. Our analysis of data made thus far cannot decide that issue. The next phase of the study will include analyses in individual women of the times, magnitudes, persistence or transience, and the like of changes in blood pressure, edema, and proteinuria. Such data will afford much more information than can be derived from the preliminary studies reported here. Although edema of the hands and face may be more common in preeclamptic than in normal women, such edema is so common in normal pregnancy as to suggest that it usually is normal. In our data, edema seems to bear no relation to hypertension or proteinuria. The triad of signs -- hypertension, proteinuria, and edema -- is generally accepted as characteristic, though far from specific for preeclampsia. Our data support Hytten's conclusion that edema should by dropped from the triad. There is some indication, however, that some edema is abnormal and that it is associated with an adverse effect when it coincides with proteinuria late in pregnancy.


Humoral control of cell proliferation: the role of fibroblast growth factor in regeneration, angiogenesis, wound healing, and neoplastic growth. The Fibroblast Growth Factor (FGF) is a mitogenic agent in the brain and pituitary of mammals. Recent investigations of the effect of FGF on diverse cell types has shown that FGF stimulates the division of cells from a wide variety of tissues of mesodermal origin including fibroblasts, chondrocytes, myoblasts, smooth muscle cells, glial cells, normal adrenal cells, and the Y1 adrenal cell line. Cell types of endodermal or ectodermal origin do not appear to be sensitive to FGF. Since FGF can be found in neural tissues and since it induces the proliferation of two cell types involved in the formation of regeneration blastemas (chondrocytes and myoblasts), we have investigated the possibility that FGF could be similar or identical to the neurotrophic factors present in nerve and responsible for the regeneration of limbs in lower vertebrates. Our results have shown that FGF could indeed substitute for the neurotropic factor and replace the nerves in inducing blastema formation and sustaining proliferation of mesenchymal cells which can differentiate into chrondrocytes and myoblasts. Since the blastema has been described as a benign tumor, the role of FGF in the formation of blastemas and benign tumors is currently under investigation. In addition to stimulating fibroblasts, FGF also has a striking growth-promoting effect on primary cultures of vascular endothelial cells. This suggests that FGF could be an angiogenesis factor. Thus, FGF, one of the most potent mitogenic agents found in tissue extracts has two properties expected of an agent which could induce tumors: it can induce blastema formation (direct mitogenic effect) and, through its mitogenic effect on endothelial cells, it could induce formation of capillaries (amplification step), permitting unlimited growth. Repair processes under FGF control will, under normal circumstances, lead to wound healing. In contrast, if cells become transplanted to the wrong environment (hormonal imbalance), growth factors such as FGF could make them proliferate in an anarchic way since negative feedback from surrounding cells will be lacking.


Immunogenicity of tumor cells modified by trinitrobenzene suflonic acid (TNBS). The ability of trinitrophenylated tumor cells to stimulate syngeneic antitumor response has been tested in 3 different tumor-host systems: A. Trinitrophenylated and inactivated Moloney induced YAC tumor cells (YAC-TNP) were able to induce the production of cytotoxic antibodies in low responding A/J mice, while inactivated YAC tumor cells (YAC-In) failed to induce such a response. Furthermore, A mice which were injected with YAC-TNP rejected 103 viable YAC tumor cells at a higher frequency than those injected with YAC-In. B. Trinitrophenylated and inactivated Gross virus induced G-35 tumor cells or Monoloney induced LSTRA cells (both syngeneic in BALB/c mice) were as immunogenic as nonmodified inactivated tumor cells. About 50% of the immunized mice survived indefinitely after injection of 103 viable tumors. Fruthermore, spleen cells from mice primed with either modified or nonomodified G-35 cells responded in vitro to G-35 in a mixed leukocyte tumor interaction and generated specific cell-mediated cytotoxic activity to 51Cr-G-35 syngeneic tumors. However, the donors of the primed cells did not produce detectable cytotoxic antibodies to G-35. C. In vitro sensitization of C57B1 spleen cells by trinitrophenylated Mitomycin C treated syngeneic EL-4 generated a stronger cytotoxic response to EL-4 cells than obtained by sensitization with Mitomycin C treated EL-4 cells alone, The superiority of the sensitizing capacity of trinitrophenylated EL-4 was readily demonstrated in conditions which were suboptimal for nonmodified Mitomycin C treated tumor. Both theoretical and practical implications of these results are discussed.


Measurement of lateral transport on cell surfaces. This paper describes the principles and recent applications of two new methods for measuring rates of macroscopic lateral transport of fluorescent-labeled particles on the surface of individual cells. Both methods are based on microfluorimetric measurements of fluorescence intensity from a small open region (greater than or equal to 1 micronm radius) on the cell surface. Transport rates are measured from the rates at which the measured fluorescence intensity changes due to entrance or departure of fluorophores from the region. One method, "Fluorescence Photobleach Recovery" (FPR), uses a brief intense pulse of light to create an initial concentration gradient over the spot by irreversible photochemical destruction of fluorophores. The rate of fluorescence recovery due to transport of unbleached fluorophores into the observation region is the primary experimental datum. The other method, "Fluorescence Correlation Spectroscopy" (FCS), is based on a statistical analysis of spontaneous fluctuations of numbers of fluorophores in the observation region and does not require a perturbation to generate an initial concentration gradient. FCS is mainly useful to measure relatively fast processes (D greater than or equal to 10(-9) cm 2/sec) in stable systems; FPR can be used to measure both slow and fast transport in less stable systems. Using both FCS and FPR, the diffusion coefficient of a fluorescent lipid probe in rat myoblast plasma membranes was measured to be D = (9 +/- 4) X 10(-9) cm2/sec over a range of at least 4 micronm. FPR was used to measure the lateral mobility of the fluorescent labeled lectin concanavalin A complexed to myoblast plasma membrane "receptors." A fraction of the complexes were immobile on the time scale of the experiment (D less than 8 x 10(-12) cm2/sec). The remainder of the complexes had effective diffusion coefficients far smaller than expected from the measurements on the lipid probe (8 x 10(-12) less than or equal to D less than or equal to 3.3 x 10(-11) cm2/sec). Moreover the mobility depended on the valence, dose, and time of occupancy of the lectin on the membrane, suggesting that an aggregation of complexes was occurring during the experiment. Cytochalasin B decreased the mobility of complexes, suggesting an influence of microfilaments on the transport process. Neither azide nor colchine affected measured transport rates. These results indicate the operation of constraints on the mobility of the lectin-receptor complexes beyond that exerted by the viscous resistance of the lipid bilayer membrane matrix. The two types of interactions revealed by our current experiments - interactions of the complexes with microfilaments and with each other (aggregation) - seem insufficient to account entirely for the low observed mobility.


Direct observation of membrane movement by electron microscopy. Motions of wet lipid bilayer membranes and plasma membranes of human erythrocytes were observed directly in an electron microscope, using the techniques of selective area diffraction, diffraction contrast imaging and electron opaque markers. The motions are measured as functions of temperature. At the liquidus state of the membrane, the lateral diffusion coefficient is deduced from the Brownian motion of the labeling particles. The coefficient is measured to be 1.1 x 10(-10) cm2/sec. for a bilayer of an equimolar mixture of cholesterol and dipalmitoylphosphatidylcholine at 20 degrees C. The value for human erythrocyte membrane at 37 degrees C is similar. At the temperature where phase separation occurs, motion is detected as the solidus domains floating on a liquidus medium. Below the transition temperature, the solidus domains move relative to one another along the domain boundaries, the drift velocity being 3 x 10(-6) cm/sec. for the above mentioned bilayer, at 4 degrees C. Together with specific labeling technique, the electron optical method may be used to study the movement of specific sites relative to the membrane, on a scale beyond the resolving power of light microscopy. The use of scanning electron microscopy is discussed.


The role of drug delivery systems in cancer chemotherapy. One approach to effective cancer chemotherapy is to maximize the exposure of tumor cells to cytotoxic drugs while minimizing the exposure of sensitive normal cells to such agents. This implies the need for control of the pharmacodynamics of anti-tumor drugs in terms of blood clearance kinetics, disposition in tissues, passage across membrane barriers, and interaction with metabolic pathways. A promising approach to pharmacodynamic control is the microencapsulation of drugs within liposomes. The clearance kinetics and tissue disposition of the drug is then dictated by the pharmacokinetic behavior of the liposomal carrier. The blood clearance rates and tissue uptake of liposomes themselves depend upon physical characteristics such as particle size and surface charge. It is also possible to promote specific interaction between cells and liposomes in vitro by preparing liposomes containing biological macromolecules such as lectin receptors. The potentialities of microencapsulation as an adjunct to chemotherapy are discussed.


Crosslinking of lectins and receptors in membranes with hetero-bifunctional crosslinking reagents. 125I-Con A was reacted with the imidoester group of methyl 4-azidobenzoimidate and isolated from excess reagents on a Sephadex G-25 column. The hetero-bifunctional crosslinking reagent has two dissimilar functional groups, imidoester and arylazide, instead of two identical functional groups found in conventional homo-bifunctional crosslinking reagents. The two functional groups react under different conditions and it is possible to react one first and to activate the other later. Here the reagents were attached to the lectins by the imidoester reactions, and the arylazides now attached to the lectins were intended for the later use to crosslink the lectins and receptors. Human erythrocyte ghosts were incubated with the activated lectins, unbound lectins removed, and irradiated with UV to photolyze arylazides, thus crosslinking the lectins to the receptors in membranes. Upon the solubilization and subsequent electrophoresis of the sample, a new band appeared on the gel. 125I-Con A was detected in band A, the new band, and band 3, one of the membrane glycoproteins, diminished in parallel to the appearance of band A. The concurrent appearance of band A accompanied by 125I-Con A and decrease of band 3 were significantly reduced, when ghosts were incubated with the activated lectins but were not irradiated, ghosts were incubated with nonactivated 125I-Con A and irradiated, or ghosts were incubated with the activated concanavalin A in the presence of alpha-methylmannoside, the lectin inhibitor, and irradiated. The inhibitor removed a significant amount of the activated lectins bound to membranes, but failed to do so the activated lectins crosslinked into band A.


Identification of a high molecular weight trans-membrane protein in mouse L cells. We have developed a new method for identifying proteins which span the plasma membrane ("trans-membrane" proteins) of mammalian cells grown in tissue culture. The method involves labeling proteins exposed on the cell surface with 125I by the lactoperoxidase technique and then preparing sealed, "inside-out" membrane vesicles (phagosomes) from the labeled cells using the polystyrene latex bead procedure. These inside-out vesicles are then treated briefly with trypsin and analyzed by SDS-polyacrylamide gel electrophoresis for the presence of 125I-labeled protein species which were degraded by proteolytic attack. Such proteins must be exposed on both the outer and inner membrane surfaces and, therefore, they must pass through the lipid barrier. This method is a general one in the sense that it is suitable for use with a wide variety of cell types, and here we show how it has been employed to prove that a particular high molecular weight polypeptide, called band 1, spans the plasma membrane of mouse L cells. Further studies of the band 1 polypeptide have demonstrated that it is preferentially exposed on the L cell surface during G1 phase of the cell cycle. Progression of cells from G1 to S is accompanied by a marked decrease in the availability of band 1 to iodination and it remains unavailable until cells re-enter G1. It is suggested that the band 1 polypeptide may be functionally involved in the regulation of cell proliferation.


Biochemical analysis of cell adhesion to a substratum and its possible relevance to cell metastasis. The evidence is reviewed that two types of cell attachment occur, depending upon the presence or absence of serum in the medium. In the absence of serum, attachment has many characteristics of a nonphysiological process. In the presence of serum, attachment occurs as a series of steps: adsorption of serum components onto the substratum, contact between the cell and substratum, initial attachment, and progressive attachments leading to cell spreading. Although there is a close interdependence of these events, they could be experimentally distinguished. Studies are reported indicating that cell spreading requires the adsorption of a specific serum glycoprotein onto the substratum surface. The relationship between cell adhesiveness and the altered behavior of malignant cells is discussed.


Isolation and preliminary characterization of that part of the plasma membrane which is apposed to the substratum. We have developed a membrane isolation technique which allows us to isolate that part of the plasma membrane which is apposed to the solid substratum (LPM) to which cells in vitro attach free of the remainder of the plasma membrane (UPM). Our evidence suggests that the UPM is essentially free of contaminating cellular organelles while the LPM may be somewhat contaminated with endoplasmic reticulum fixed to it during the isolation procedure. Characterization of the peptides of the UPM and LPM suggests that some membrane components are nonrandomly distributed to one or the other membrane fraction while the bulk of the membrane peptides appear to be present in both membrane fractions; Membrane components labeled with 3H-fucose or 3H-glucosamine show a 3--5-fold higher specific activity in the LPM than in the UPM. A number of iodineateable surface components, in particular the LETS protein, show a preferential localization to the LPM. The development of this membrane isolation procedure should allow us to begin investigating the molecular basis of differences in cell-substratum adhesion and cell motility, two functions assigned operationally to the LPM.


Patching, microvilli, and the agglutination of normal and transformed cells. Transmission and scanning electron microscopy were used to study possible structural correlates in the process of agglutination of several types of normal and transformed cells by Concanavalin A. In parallel studies we found that post-confluence inhibition of cell division and agglutiniability of cells by Concanavalin A were not correlated with patching of surface bound lectin molecules as determined with a hemocyanin marker. Transformed cells growing in monolayer cultures were found to have many more microvilli than the corresponding normal cells. However, when cells were brought into suspension with EDTA, all cells developed numerous microvilli and we were not able to distinguish between agglutinable and nonagglutinable cells on the basis of morphological appearance. Cells agglutinated by Concanavalin A had numerous interdigitated microvilli at points of cell-cell contact. The appearance of spontaneously agglutinated cells and lectin agglutinated cells was very similar with respect to the involvement of microvilli in cell-cell attachments, and labeling studies with hemocyanin indicated that Concanavalin A bound to microvilli is rapidly cleared from these surface specializations in a manner analogous to that observed with patching of surface bound lectin. Several lines of SV-40 transformed fibroblasts were shown to be considerably more spontaneously agglutinable than untransformed cells. These results indicate that Concanavalin A may amplify an intrinsic membrane property common to many transformed cells that is expressed as an increase in the rate of adhesion of suspended cells. It is proposed that the membrane change detected by the agglutination reaction may also be involved in the loss of post-confluence inhibition of cell division and growth of transformed cells in semisolid media, due to a surface interaction that allows transformed cells to use each other as growth substrata.


Therapeutic relationships between DNA synthesis and repair, membrane differentiation, and organ-specific immunotherapy in neuroblastoma. The mouse neuroblastoma cell system (MNB) is of interest to both neurobiologists and cancer researchers because of its capacity to differentiate, with the consequent loss of some properties classically associated with malignancy. The effects of chemotherapeutic agents on MNB cells are variable; in general, cell cycle-specific agents will frequently induce differentiation, leaving viable surviving cells, while cell cycle nonspecific agents are toxic to both dividing and nondividing MNB cells. X-rays appear intermediate in that they are toxic to both cell populations, but survivors tend to resemble cells treated with cell cycle-specific drugs. Differentiated MNB cells apparently lose their capacity to repair some forms of DNA damage and this loss may be associated with their sensitivity to DNA damaging compounds. MNB cells are also susceptible to immunological lysis, particularly antibody-dependent cellular cytotoxicity. Integration of these diverse modes of MNB cell killing is of great interest because of the close resemblance of this murine tumor to human cancers in which cell differentiation is also partially membrane-mediated an indepth study of MNB cell surface receptors may have general relevance in the theoretical approach to cancer treatment.


Independent control of the expression of several membrane-associated antigens of murine leukemia cells: metabolism and response to specific antiserum. The effect of specific antisera on the metabolic rates of thymus-leukemia (TL), H-2a, and tumor-associated antigens of ASL-1 and RADA-1 cells, two murine leukemia cell lines, were determined. The metabolic half-life of each antigen was distinct from the others examined. The half-life of TL antigens was 18 hr; in cells exposed to TL antiserum, it changed to 9 hr. In RADA-1 cells, the half-life of TL antigens was 16 hr; in the presence of TL antiserum it became 4 hr. The half-lives of H-2a antigens and the tumor-associated antigen were unaffected by specific antiserum. Somatic hybrids of ASL-1 or RADA-1 cells were formed with LM(TK)-cells, a thymidine kinase deficient mutant of mouse L cells. Hybrid cells formed TL antigens, but unlike their parental cells their half-life of expression, approximately 30 hr, was unaffected by TL antiserum. Hybrid cells failed to undergo antigenic modulation under conditions more stringent than required to stimulate the modulation of ASL-1 or RADA-1 cells. The hybrids formed the tumor-associated antigen of their murine leukemia parental cells; however, the metabolic rate of the tumor antigen in hybrid cells was defferent than the metabolic rate of the analogous antigen in parental cells. Hybrid cells formed H-2 antigens of both parental sources, and possessed a hybrid karyotype. The half-life of H-2 antigens, approximately 26 hr, was the same both in parental and hybrid cells. H-2a antiserum had no detectable effect upon the metabolism of TL antigens in hybrid or parental cells; nor did TL antiserum have an effect upon the metabolism of H-2a antigens.


Production of hypercalcemia in the chick embryo by an extract of Solanum malacoxylon. White Leghorn eggs were injected on the 15th day of incubation with various doses of an acqueous extract of Solanum malacoxylon (SME). Most of the embryos died after the injection of 0.2 ml but the dose of 0.1 ml was well tolerated. The concentration of calcium in the sera from 15-day embryos injected with 0.1 ml SME was determined. Three hr after the injection the concentration of calcium had increased significantly; this increase lasted for at least 3 hr more but had disappeared 12 hr after the injection. It is suggested that this hypercalcemia may be produced by a water-soluble analog of 1,25-(OH)2D3 the presence of which has been demonstrated in the SME by other authors. It is also assumed that the mortality produced by the higher doses may be related to the hypercalcemia.


Subclinical trichostrongylosis in growing lambs produced by continuous larval dosing. The effect on performance and certain plasma constituents. Three groups of eight-four-month-old worm-free lambs were used to investigate the effect of Trichostrongylus colubriformis infection on growth rate, food intake, and concentration of plasma constituents. Groups ALC and ALI were fed ad libitum, the latter being dosed daily with 2500 infective larvae for 14 weeks. Lambs in group PF were paired to individuals in group ALI and offered the same quantity of food as the infected pair consumed. Hypophosphataemia and hypoalbuminaemia developed in ALI at week 3 and hyperglobulinaemia was present from week 6. There was no significant difference in plasma calcium, protein, urea or glucose concentration between the three groups at any stage. No clinical signs of parasitism were seen in seven of eight ALI lambs and egg counts were generally less than 2000 epg. Worm burdens of 1500-82,900 were found at slaughter. Group weight gain was only 50 per cent of PF lambs which received the same digestible energy intake. Group ALI consumed 15-5 kg dry matter per kg gain in bodyweight compared with 8-6 kg/kg and 9-8 kg/kg for ALC and PF respectively. The infections resulted in extensive villous atrophy and flattening of the intestinal mucosa. Bone growth was arrested and osteoporosis present in five group ALI lambs. The possible use of plasma constituents, particularly phosphorus, as aids for the diagnosis of the early stages of trichostrongylosis in the field is assessed.


The effects of bumetanide on renal function and blood composition in sheep. Respones to bumetanide were studied in five ewes. During ADH infusion urine flow increased from less than 1-0 to approximately 11-5 cm3 min-1 within 30 min of intravenous injection of 0-02 mg kg-1 bumetanide and returned to approximately 2-0 cm3 min-1 within 3 h of dosing. The diuresis was accompanied by large increases in sodium and chloride excretion and smaller increases in potassium and free hydrogen ion excretion. Bicarbonate excretion and TCH20 were reduced. Plasma potassium and chloride concentrations decreased slightly while arterial bicarbonate pH and pCO2 slightly increased. A transient increase in GFR and RPF was followed by a small reduction in GFR. No change in CH20 was observed after bumetanide injection during water diuresis. Increasing the dose of bumetanide over the range 0-002 to 0-20 mg kg-1 resulted in more pronounced and prolonged responses. The results show that bumetanide is a potent diuretic in sheep with its main site of action on the ascending limb of Henle's loop.


Preliminary observations on the use of the capillary flocculation test for the diagnosis of heartwater (Cowdria ruminantium infection). A capillary flocculation test was developed to diagnose heartwater disease of ruminants. Antigen was prepared from the brains of cattle and goats highly infected with Cowdria ruminantium. Sera were obtained from experimentally infected ruminants which either recovered naturally or with the aid of oxytetracycline treatment. Antibodies were first detected one to two weeks after clinical recovery or after treatment, and persisted for periods varying between one and four weeks. Control sera collected from cattle (sheep) and goats in the Netherlands where heartwater does not occur, or from animals serologically positive for Anaplasma marginale or Eperythrozoon ovis infections, did not react to the test.


The isolation of ovine lymphocytes and granulocytes from whole blood using hydroxyethylcellulose. Sheep erythrocytes do not aggregate spontaneously but will sediment when mixed with a solution of hydroxyethylcellulose. The resulting leucocyte-rich supernatant can be used in the preparation of purified lymphocyte and granulocyte suspensions.


Histological development of the small intestinal mucosa in the ovine fetus. Histological changes in the small intestine of 85 ovine fetuses were studied, with particular reference to the mucosa. In 24-day-old fetuses the endoderm of the intestine consisted of a single layer of epithelium. By the 26th day the epithelium was flattened and stratified. The first evidence of rudimentary villus formation was noted in 39-day-old fetuses. Intestinal glands were first observed at 56 days. Other mucosal structures were present by 101 days. At birth the intestinal mucosa was fully mature.


Pharmacokinetic interpretation of erythromycin and tylosin activity in serum after intravenous administration of a single dose to cows. The distribution and elimination kinetics of erythromycin and tylosin, which are macrolide antibiotics, were studied in healthy cows. A single dose (12-5 mg/kg) of drug was administered as an intravenous bolus, and blood samples were collected at precisely timed intervals. The standard cylinder plate bioassay method using Sarcina lutea as test organism was employed to determine antibiotic activity in the serum. The results suggested that these drugs are distributed in at least two kinetically distinct body compartments. By use of established mathematical techniques, values were assigned to the individual rate constants controlling distribution between the central and peripheral compartments and to the rate constant  controlling overall elimination (beta) of each drug from the body. The calculated overall tissue to serum drug level ratios (k12/k21) after apparent distribution equilibrium was attained were 2-28 and 2-05 for erythromycin and tylosin, respectively. The half-life (mean+/-SD) of erythromycin was 3-16 h+/-0-44, while that of tylosin was 1-62 h+/-0-17. The total body clearance (ml/kg/min) values were 2-88+/-0-47 for erythromycin and 7-8+/-2-95 for tylosin. Analogue computer simulated curves of the antibiotic levels in the central and tissue compartments as wel as an elimination curve were generated. The tissue level of erythromycin reached a peak of 43 per cent of the dose at 67 min. At 6 h, the percentages of the dose of erythromycin in the central and tissue compartments and eliminated were 6, 19 and 75, respectively. The peak level of tylosin in the tissue compartment (26-5 per cent of the dose) was present at 30 min. At 4 h, 1 and 5 per cent of the dose were contained in the central and peripheral compartments, respectively, while 94 per cent had been eliminated. This single dose study provides information which is essential for the design of a satisfactory dosage regimen.


The qualitative assessment of glycosaminoglycans in the canine intervertebral disc using a critical electrolyte concentration staining technique. Through the use of a critical electrolyte concentration staining technique, the glycosaminoglycans (GAGs) in the nucleus pulposus region of the canine intervertebral disc were arbitrarily identified as "hyaluronic acid", chondroitin sulphate and keratan sulphate. Approximate estimates of GAG concentration could be qualitatively deduced by determining the appropriate GAG "ALCIANOPHILIC INDEX". This index was considered to be an effective qualitative adjunct to chemical quantitation of GAGs in the intervertebral disc.


Swine dysentery: protection of pigs by oral and parenteral immunisation with attenuated Treponema hyodysenteriae. An attenuated strain of Treponema hyodysenteriae was used to immunise 18 pigs in three experiments. Live attenuated spirochaetes were dosed orally and injected intra-peritoneally, and killed spirochaetes were injected intramuscularly with adjuvant. The vaccinated pigs, which developed high serum agglutination titres against T hyodysenteriae, and 18 unvaccinated litter-mates were repeatedly challenged with virulent T hyodysenteriae. Nine vaccinated pigs and 16 control pigs developed typical swine dysentery.


Electrophoretic variants of alkaline phosphatase in normal human populations. Polyacrylamide gel electrophoresis of sera obtained from normal individuals shows an incidence (33%) of double and triple bands of alkaline phosphatase in the beta-lipoprotein zone in addition to the usual ones near beta-globulin. The correlation between the occurrence of a slow moving band in addition to the normal one, of different intensities, p+ and p++ with O and B groups has been further confirmed. No relationship was observed between the width or the number of bands with the total amount of alkaline prosphatase as determined biochemically.


Modifications in some rat liver cell components following stimulation with isoprenaline (a cytospectrophotometric, microrefractometric and cytoelectrophoretic study). The liver cell is a quite interesting model for the study of several cytophysiological problems. Proper suspensions of isolated liver cells can be obtained which can be conveniently studied by means of quantitative microtechniques. Several cytochemical and cytophysical techniques (cytospectrophotometry, microrefractometry, and cytoelectrophoresis) were employed for elucidating the effects on the stimulation of the liver cell with high doses of isoprenaline, an amine which is known to produce hypertrophy and hyperplasia in various organs with effects also at the genetic and metabolic level. The following data were collected during the postnatal development of rats up to the 70th day of life: 1) DNA content per nucleus; 2) total dry mass per cell; 3) cellular electrophoretic mobility in connection with the sialomucinic component of the membrane. The process of polyploidization of the liver cell (typical of this life period) was generally accelerated; in this connection, an early appearance of binucleate cells and subsequent significative variations in their incidence were observed. This fact is important as the binucleate cells should represent an alternative intermediate step in the polyploidization phenomenon. At the same time, marked, although transient, signs of cellular hypertrophy were detected during a rearrangement of the hepatocyte dry mass, where the values tended to a multimodal distribution; in particular, IPR appeared to favor the disappearance of cells with a lower mass to the advantage of those with an intermediate mass. The study of electrophoretic mobility evidenced the role of the sialomucinic component of the membrane in the changes occuring in the parenchyma: indeed, this component exhibited an increase, thus causing an acceleration of the mobility similar to the one observed in actively proliferating cell populations. Such change persists even long after the IPR stimulus has ended and, at any rate, beyond the immediate phase of DNA synthesis and the appearance of binucleate cells.


Prevalence and distribution of schistosomiasis in Indonesia: a review. The prevalence and distribution of schistosomiasis in Indonesia is given, with the emphasis on the current data. An extensive investigation was started in 1971. Control measures became desirable because of development schemes in and around the endemic areas, thus increasing the possibility of the spread of the infection. This investigation consisted of: a study of prevalence, distribution, and intensity of the infection in man and animals; clinical studies, treatment and follow-up; and epidemiological studies. A comparison was made between the results of different workers. In addition to the only known endemic area at Lake Lindu, another endemic area was discovered recently at Napu Valley, situated 50 km southeast of Lake Lindu at an altitude of 1200 meters. Surveys in other areas gave negative results. Nine species of wild and domestic animals were found positive. The intermediate host was discovered in 1971 and described as Oncomelania hupensis lindoensis. This snail is widely distributed in the endemic areas.


Schistosomiasis in Cambodia: a review.

Schistosomiasis in Cambodia: a review. Human schistosomiasis has been known in Cambodia only since 1968. In 1968-1970, many cases were detected in the provincial capital of Kratié. Infection seemed to be confined to the ethnic Vietnamese fishermen who inhabited raft houses (= floating villages) on the Mekong River at Kratié. Overall prevalence in fishermen of all ages was between 7 and 10%. In the children of fishermen between the ages of 1 to 14, the prevalence was between 14 and 22%. Transmission was apparently limited to floating houses stationed more or less permanently near shore and connected to each other in a chain. It is believed that transmission occurred only in the areas of still water which were created between raft and shore. The principal focus of schistosomiasis in Cambodia appears to be Kratié. Only a few cases have been detected elsewhere in the country. The parasite is undoubtedly identical with the Schistosoma reported from humans and dogs at Khong Island, Laos. However, the transmitting snail in Laos, Lithoglyphopsis aperta, has thus far not been reported from the Mekong River in Cambodia.


Some aspects on the ecology and biology of Oncomelania hupensis lindoensis. Schistosomiasis is known to be endemic in the lake Lindu area since 1937 (Brug & Tesch, 1937). Investigations carried out later between 1940 and 1942 (Bone et al., 1942) failed to find molluscan intermediate host. It was not until April 1971 that the first specimen of Oncomelania was found (Carney et al., 1972). In August of the same year the first focus was discovered at Paku (Hadidjaja et al., 1974). Further investigations revealed 50 more foci in the lowlands surrounding the lake. A survey of the habitat in the Napu Valley revealed 15 more Oncomelania colonies (Crney et al., in prep.). The morphology studied by Davis and Carney (1973) showed that this snail has a close resemblence to O. h. chiui and O. h. quadrasi. It was given the subspecies name Oncomelania  hupensis lindoensis. Snail cultures maintained according to Davis' method (1971) were done in the laboratory of the Department of Parasitology, Faculty of Medicine, University of Indonesia. Diatoms and algae were given as food. Biology of the snails concerning the temperature, hymidity, mortality rate of the snail or survival rate and also the living and egg laying habits of the snails were described.


Preliminary observations on the biology of the Indonesian strain of Schistosoma japonicum: animals and oncomelanid snails. Laboratory animals and subspecies of Oncomelania hupensis were exposed to experimental infections with a strain of Schistosoma japonicum from the Lindu Valley, Central Sulawesi, Indonesia. All laboratory animals given 50 cercariae were suspecptible to infection with the greatest number of worms being found in mice followed by Wistar rats, Long Evans rats, Mongolian gerbils, wild rats, hamsters and guinea pigs. Rabbits and the Taiwan monkeys given larger numbers of cercariae were also susceptible to infections. Adult worms were found to reach the largest size in the rabbit and Taiwan monkeys but many worms from rats were immature. Eggs from the Taiwan monkey were larger than those from a dog and from mice. Six subspecies or geographic strains of Oncomelania hupensis were exposed to 3 to 5 miracidia of the Indonesia strain of Schistosoma japonicum and only Oncomelania hupensis lindoensis and Oncomelania upensis chiui from Taiwan were susceptibile and produced cercariae while Oncomelania hupesis formosana from Changhua, Ilan and Kaohsium countries of Taiwan as well as Oncomalania hupensis quadrasi from the Philippines were considered refractory to infection.


Control of Schistosoma japonicum infection in Lindu Valley, Central Sulawesi, Indonesia. In Indonesia, schistosomiasis is presently confined to two endemic areas in Central Sulawesi; Lindu (1,500) and Napu (5,000 inhabitants) valleys. Because of various development schemes now underway, it is feared that the natural balance which existed for many years between the parasite, the snail intermediate hosts and man, will be upset and will place some 70,000 people of the adjoining Palu and Palolo areas at risk. Measures are being taken to control and prevent the spread of the disease. A pilot control programme is planned for two years in the village of Anca in Lindu with a population of 391 and a prevalence rate of 70.5%. Langko village with a population of 464 and a prevalence rate of 53.7% will be utilized as the comparison area. Baseline data on human, malacological and animal reservoir hosts are being collected and control operations are anticipated to commence in July 1975. Measures to be applied to control schistosomiasis in the order of priorities are: (a) agro-engineering or modification of the environment; (b) environmental sanitation through the provision of adequate water supply and construction of latrines; (c) mollusciciding of remaining snail infested areas; (d) chemotherapy, and (e) health education campaign. At the end of the two-year control programme, the following activities will be carried out to determine the degree of intervention achieved; (a) human data: calculation of prevalence rates, incidence rates, and changes in the intensity of infection based on quantitative egg counts; (b) malacological data: changes in the number and extent of snail foci; snail density, and snail infection rates; (c) reservoir hosts: changes in the prevalence rates among domestic and wild animals. Calculation of reclaimed areas and increase in agricultural production will also be assessed together with the overall cost/benefit analysis of the project undertaking.


Agro-engineering and sanitation improvement in the control of schistosomiasis japonica in the Philippines: a review. Measures that would change the habitat of the snails were found to prevent its breeding. Among these are clearing and drainage of waterlogged areas; filling of depressions where filling materials are available; ponding of areas which cannot be drained, and improved rice culture. The degree of success in snail control depends to a large extent on the amount of change brought about in the habitat. The more radical the change, the greater the reduction in snail density. It can be expected that improvement in sanitation in the form of toilet construction and use, provision of safe water supply, building of footbridges and the control of stray animals will bring a further decline in the transmission of the disease. Studies have shown that perfect sanitation in the form of toilet construction and use will reduce transmission by about 75%, the other 25% being contributed by lower mammals. Agro-engineering control measures are presently being carried out intensively in 7 town of Leyte, with food assistance from the UN/FAO World Food Program being given to volunteer workers as incentives for them to work. Snail evaluation after 2 years has shown a snail reduction by 72% in the areas covered. It may be mentioned here that sanitation improvement, especially latrine construction, is an ongoing program of the Department of Health in all rural areas.


A coxsackievirus type A24 epidemic conjunctivitis in Brunei. The paper reports on a coxsackievirus type A24 epidemic of acute conjunctivitis in Brunei. The role of the Singapore Epidemic Conjunctivitis 1970 (coxsackievirus type A24) virus in the new disease syndrome variously known as the "Epidemic Haemorrhagic Conjunctivitis", "Picornavirus Epidemic Conjunctivitis" and "Acute Haemorrhagic Conjunctivitis" is again established.


A comparison of the efficiency of the Nuclepore and Millipore filtration systems for detecting microfilariae. Using Brugia pahangi or Dirofilaria immitis as the test organisms no significant difference could be detected between Nuclepore and Millipore filters. It was found that 0.7% of microfilariae passed through the Millipore and 1% through the Nuclepore filters. No microfilariae were lost from the Nuclepore membrane during the staining process.


Autorhythmometry: leads from single-sample medical check-ups toward a health science of time series. Starting from the definition of health as given by the WHO, the authors emphasize that rhythms of biological variables should be taken into account if one is to arrive at a positive and individual definition of the concept of health. The evaluation of a single datum spot check of physiological functions does not permit to quantify health in dynamic terms whereas this may become possible when the rhythmic quality of these variables, according to a spectrum of characteristic frequencies, has been assessed. Rhythmometry provides for appropriate reference standards as regards both the population in general and the physical conditions of the same subject during certain spans in the (prospective) life history (spans selected according to consideration of risk and hence cost and benefit at a given age). The authors therefore stress the importance of rhythmometry, thanks to which the time course and other peculiarities of any biological phenomenon can be evaluated by obtaining serial measurements, objectively quantifying their characteristic features, and working out special models with the aid of computers. Of special interest, particularly for the evaluation of reference standards, is autorhythmometry (AR), to be used at least for certain variables. This is the method by which each subject studies himself, performing a certain number of measurements in the course of the day (or month or year) of his body temperature, blood pressure, cardiac rhythm, grip strength, etc. In AR, the subject takes an active part in the study of his condition of health and it has been shown that in the majority of cases these measurements are done with the utmost accuracy and precision, providing that the purpose of the operations to be performed has been adequately explained. The wide spread use of AR, during more or less extended periods in a lifetime, would permit the assessment of the normal situation for each individual and thus offer the possibility of diagnosing any disorder at its very beginning; it would thus be of great prophylactic value. The authors refer to the example of arterial blood pressure; widely different values for the normal levels can be found in the texts of different authors. They also show that a certain presure may be normal for a given subject at a certain time of day and be a sign of illness for another subject, or even for the same subject at a different ime. The authors suggest the introduction of AR in the curriculum of secondary schools and into the routine for outpatients and inpatients. This practice would increase the availability of information on public health at a lower cost. AR may be very usefully applied to chronotherapy: it is a well-known fact that there are rhythms of sensitivity and therefore rhythms of toxic as well as therapeutic effects for various drugs. These can be dove-tailed in such a way as to work out, for individual cases, a time for administration at which the therapeutic effect is at its maximum and the toxic one at its minimum...


Cord blood cholesterol, triglycerides and lipoprotein electrophoresis in 124 Italian infants. Total cholesterol (TC), triglycerides (TG), and lipoproteins (by electrophoresis on agarose gel) were determined in the cord blood of 124 Italian infants (Verona area). The mean TC and TG values, when compared with the values reported in other studies, turned out to be remarkably uniform, suggesting common genetic determinants in the modulation of blood lipids; no sex differences were  observed. The TG distribution curve was skewed, overlapping the adult pattern. Cord blood TC and TG were not modified by the presence of perinatal factors. Both beta and alpha bands (on agarose gel electrophoresis) were present in  all the cases. The pre-beta band was clearly detectable in 90% of the cases; it was barely visible for TG values below 20 mg/100 ml; occasionally a discrepancy between the intensity of the pre-beta band and the cord blood TG was observed, indicating a variable lipid composition of very low density lipoproteins (VLDL). In 4% of the cases a small band at the origin of the electrophoretic run was observed, consistent with the presence of chylomicrons. In the serum of both a newborn infant and its mother we detected a double band migrating in the pre-beta region. This finding confirms the hypothesis of a familial transmission of this abnormality.


Leptospirosis in Malaysia: a common cause of short-term fever. A study of 1,437 unselected febrile patients in rural Malaysia yielded a diagnosis of leptospirosis in 86 (6.0%). The clinical syndrome was mild to moderate in all cases, jaundice was observed in only 2 (2.3%) and no deaths were documented. The diagnosis was not clinically obvious in most cases, and it is apparent that many infections must be going unnoticed at present.


Hydrogen sulphide production as an aid to the identification of Vibrio parahaemolyticus. In this study 18 strains of Vibrio parahaemolyticus from food and 8 from humans were tested for hydrogen sulphide production on various modifications of Russel's Triple Sugar slopes and on TSI. All strains showed a characteristic surface browning on RTS with Andrade's indicator. This was not seen when RTS with phenol red as indicator or TSI were used. Appearance of this phenomenon allows unknown strains to be suspected as being Vibrio parahaemolyticus.


Angiostrongylus malaysiensis from Tuaran, Sabah, with reference to the distribution of the parasite in Malaysia. A survey of Angiostrongylus malaysiensis among wild rodent and molluscan hosts was made in the Tuaran Central Agricultural Research Station and within the vicinity of Tuaran, Sabah. Three of 19 Rattus rattus diardii, one of 2 R. exulans and one R. argentiventer were found naturally infected with the parasite. In this survey 56 of 382 molluscs comprising of Pila scutata, Achatina fulica and two species of land slugs, Laevicaulis alte and Microparmarion malayanus, were found naturally infected with the parasite. Samples of larvae from each of these molluscs were experimentally transferred to laboratory albino rats and adult worms consistent with A. malaysiensis were recovered. Comparison of the rat hosts and the molluscan intermediate hosts of the parasite in Peninsular Malaysia, Sarawak and Sabah was made, and the finding of A. malaysiensis in Tuaran is the first report of the parasite from Sabah. The distribution of the parasite throughout Malaysia is discussed. Observation on the human consumption of the freshwater snail, P. scutata, was made. Although the infection rate of this snail is low compared with other molluscan hosts examined. The importance of this mollusc as a potential source of human infection should not be overlooked. Hospital records for 1974 and 1975 were examined and clinical human angiostrongyliasis was rarely recorded in Sabah.


Nuclear medicine computing. Where we have been, where we are and where we are going. Demand for the newest and most elaborate Nuclear Medicine equipment is at an all time high. Never has there been more to offer than now with such improvements as large field of view, high resolution, whole-body capability and so on. The dedicated minicomputer systems that are available to go with these latest imaging devices are equally impressive. Still, the headaches associated with putting together a full capability camera/computer system are numerous. Things just do not seem to go together the way they ought to. If we are to truly get the most value out of our new equipment, we must put tremendous work loads on our clinical staff by expecting them to use very awkward and poorly configured systems in which several complicated steps are required to to produce the finished product ready for the reading room. The relatively low usage factor which most clinical Nuclear Medicine computer systems experience is not surprising when we consider the ridiculous way in which these systems are configured. It is time for a little human engineering to be introduced into the design process. Unfortunately, this proliferation of equipment is wasteful of money as well as the operator's time. It would make more sense to consolidate the multitude of displays and controlling elements into a single console which would allow a single operator to perform all necessary data processing operations quickly and interactively.


Amino-oxidase and dermal connective tissue in scoliosis. The amino-oxidase and collagen content of dermal tissue was evaluated in 10 patients with severe idiopathic scoliosis and in a control group of 7 patients with poliomyelitic scoliosis, that were to undergo surgical correction of their skeletal deformity. A greater dermal content of neutral salt souble collagen was found in the patients with idiopathic scoliosis, compared with the control group. Statistically the difference was highly significant. Mono-amino-oxidase activity, however, was found to be significantly decreased in dermal extracts obtained from patients affected by idiopathic scoliosis in comparison with controls. The involvement of mono-amino-oxidase in the crosslinking of collagen and the possible classification of idiopathic scoliosis as a systemic disease of connective tissue are discussed.


Parasitological survey in Gorontalo North Sulawesi, Indonesia. A survey for blood and intestinal parasites was carried out in the municipality of Gorontalo on the Minahasa peninsula of North Sulawesi. A total of 156 stool specimens were obtained from 83 males and 73  females. Trichuris trichiura, Ascaris lumbricoides, hookworm, unidentified dicrocoeliid-like ova and Entamoeba coli, in that order, were the most common intestinal parasites detected. Other intestinal parasites found less frequently were Entamoeba histolytica, Iodamoeba bütschlii, Endolimax nana, Giardia lamblia, Enterobius vermicularis and Chilomastix mesnili. Brugia malayi microfilaremiar were detected in 6% and Plasmodium falciparum in less than 1% of the population sampled.


Observations on the breeding habitats of Aedes aegypti (L.) in Jakarta, Indonesia. A one-year study was done of the breeding habitats of Aedes aegypti (L.) and of the water storage habits of the inhabitants in four crowded districts of urban Jakarta. Immature mosquitoes were found in or near houses in containers of relatively clean water used for drinking or bathing purposes. An average of 185 containers were found per 100 houses, of which 60 were positive for Aedes immatures, resulting in a Container Index of 32%. The mean potential water storage capacity per house was 173 liters of which only 92 liters of water was actually being stored at any one time. Water jars were the most common containers found, but bak mandi (cuboidal or oblong concrete reservoirs) held more water per container. Total water storage per house in bak mandi was twice that of water jars and ten times that of drums, which were uncommon. Ant traps and other miscellaneous containers were unimportant for either water storage or mosquito production. A mean of 0.93 pupae per  house was found, pupal production indoors being ten times than outdoors. Indoor water jars produced more pupae per house than all other containers combined. The infestation rate of covered containers was significantly higher than that of uncovered containers, perhaps because loose-fitting lids allowed entrance of gravid females to the attractive darkened interior of the container.


Reactivation studies on organophosphate inhibited human cholinesterases by pralidoxime (P-2-AM). There is biochemical and clinical evidence that P-2-AM (Pyridine-2-Aldoxime Methiodide, Pralidoxime) does not reactive human acetylcholinesterase inhibited by either Malathion or Malaoxon. In vitro studies using Pralidoxime iodide up to ten times the recommended concentrations, produced insignificant reactivation of cholinesterases inhibited by Malathion or Malaoxon. This was observed inspite of prolonged exposure of the inhibited cholinesterases to the oxime. The value of Pralidoxime as a reactivator of phosphorylated cholinesterases is therefore in doubt, and should not be used in preference to large doses of atropine and other supportive treatment in poisoning by organophosphate pesticides.


Carcinoma of the cystic duct associated with opisthorchiasis. Four patients who had obstructing carcinoma of the cystic duct and who presented themselves with enlarged and palpable gall bladders but without jaundice are reported. All patients came from endemic areas of opisthorchiasis and had evidence of Opisthorchis infection by peritoneoscopic and surgical findings. All but one had Opisthorchis eggs in the stool. The pathogenesis and management was discussed.


Comparative growth of Malay, Chinese and Indian school children in Malaysia. The weights and heights of 3,312 Malaysian primary school boys and girls, aged 6 to 11 years, belonging to various ethnic groups in Malaysia were measured. On the whole, the Chinese children were taller and heavier than the Malay and the Indian children who were the least heavy among the three ethnic groups. Economically the Indians were the poorest among the three ethnic groups and they also had the largest family size. When the household incomes were taken into consideration it was found that the growth achievement of the higher income children was better than that of the poorer children, irrespective of their ethnic groups. It is interesting to note that, although the Indian children as a whole, were the least heavy of the three ethnic groups, yet the growth achievement of the higher income Indian children was similar to that of the higher income Chinese children. The differences in growth achievement of the various ethnic groups are probably due to environmental differences, rather than genetic differences. It seems likely that Malaysian children of different ethnic groups (Malay, Chinese and Indian) can attain similar statures if environmental conditions are similar.


Intestinal and blood parasites of man in Bireuen and Takengon, Aceh Province, Sumatra, Indonesia. A survey for blood and intestinal parasites was carried out in Aceh Province of North Sumatra, Indonesia. A total of 348 stool specimens were obtained from 167 males and 181 females ranging in age from 6 months to 70 years. Over 98% of the population sampled were found infected with at least one intestinal parasite. Ascaris lumbricoides, Trichuris trichiura, hookworm and Entamoeba coli, in that order, were the most common parasites detected. Other intestinal parasites found less frequently were Entamoeba histolytica, Iodamoeba bütschlii, Entamoeba hartmanni, Endolimax nana and Giardia lamblia, Brugia malayi microfilaraemias were detected in 2% of those examined and only in the coastal villages of Cot Ketapang and Rusip Dayah. No malaria was found.


Prevalence and zoonotic potential of Ancylostoma ceylanicum in cats in Thailand. Ancylostoma ceylanicum and Ancylostoma caninum were found in cats from Prachin Buri, Thailand, with infection rates of 92% and 23%, respectively. In this survey, 75% of cats were infected with A. ceylanicum alone, the rest had mixed infections of A. ceylanicum and A. caninum. The worm burden range in 26 cats for A. ceylanicum and A. caninum were 1 to 83 and 1 to 10, respectively. For A. ceylanicum, both males and females were found in the gut from the first part of duodenum to rectum. In the case of A. caninum the distribution was not constant. The sex ratio between male and female A. ceylanicum was 1:1.4. The egg count for A. ceylanicum was in the range 31-150 per gram of faeces (mean 70). The zoonotic potential of these parasites was discussed.


Endemic goitre in Sarawak, Malaysia: I. Somatic growth and aetiology. A comparative epidemiological and anthropometric survey was conducted among Ibans, the largest indigenous ethnic group in Sarawak, in three regions where the endemicity of goitre exhibited marked differences , to assess the effect of endemic goitre on somatic growth. In the Ai river region the prevalence of goitre was 99.5%; 35% having grade 3 goitres, 55% grade 2 goitres and 9.5% grade 1 goitres. At Rubu the prevalence of endemic goitre was 74%; 3% having grade 3 goitre, 16% grade 2 goitre and 55% grade 1 goitre. In the Bajong region relatively few people were detected with goitre and most of these had migrated from other regions. Neurological cretinism was estimated at 3.6% in the severely goitrous Ai river population but was not detected in the other regions. Anthropometric data obtained from the three adult populations did not reveal any statistically significant differences in the following parameters: weight, height, weight/height ratio, height/sitting height ratios, head circumference, scapular skinfold thickness and left mid arm muscle circumference. The haemoglobin, serum total protein and serum albumin concentrations were similar in the three populations. It is concluded that endemic goitre occurs with  a frequency of close to 100% in certain Iban populations which represents one of the highest incidences of endemic goitre in the world. Neurological cretinism is common in this population. Our observations suggest that body proportions and somatic growth do not vary among similar ethnic populations exhibiting greatly different endemicity of goitre. Although no iodine balance studies were performed, assessment of diets suggested that iodine deficiency is a significant contributory factor in the development of endemic goitre in Sarawak. Urgent attention to iodine supplementation is indicated to prevent the development of endemic goitre and neurological cretinism.


Pralidoxime as an insignificant reactivator in severe anticholinesterase (organophosphate insecticide) poisoning. In acute severe anticholinesterase poisoning by organophosphate compounds, pralidoxime (P-2-AM, pyridine-2-aldoxime methiodide) used in the recommended doses, intravenously, has not been shown to reactivate the inhibited cholinesterase, as evidenced both clinically and biochemically. In vitro studies using pralidoxime iodide up to ten times the recommended concentrations, produced insignificant reactivation of cholinesterases inhibited by the organophosphate insecticide Bidrin (di-methyl-3-hydroxyl-N, N-dimethyl-crotonamide phosphate). This was even so despite prolonged exposure of the inhibited cholinesterases to the oxime. The value of pralidoxime as a reactivator of phosphorylated cholinesterases is therefore in doubt, and should not be used in preference to large doses of atropine and other supportive treatment in poisoning by organophosphate insecticides.


Chronic industrial exposure to lead in 63 subjects. I. Clinical and erythrokinetic findings. Clinical, biochemical, haematological and erythrokinetic studies were performed on 63 adult males with prolonged lead exposure. Their most common symptoms and findings were abdominal pain (62%), gingival lead lines (48%), headache and/or dizziness (33%), muscle cramps (32%), anaemia (19%), and fatigue (18%). Colicky abdominal pain (27%) and gingival lead lines correlated with urinary lead excretion. Anaemia was mild, but more frequent in the subjects with the greatest urinary lead excretion. Other associated findings were: higher reticulocyte counts and more basophilic stippling of the RBCs, more sideroblasts and greater erythroid hyperplasia of the bone marrow, more reduction in 51Cr-tagged RBC survival time, smaller RBC mass, a more rapid plasma iron clearance, a greater plasma iron turnover and greater utilization of 59Fe in subjects with urinary lead excretion of greater than 100 microng/day in comparison with the remainder and normal controls. These findings suggest that minimal chronic exposure to lead causes an increased haemolysis with resulting increased production of erythrocytes.


The changes of the hair roots in correlation to the clinical status of the nephrotic syndrome. The examination of the hair roots were performed by a modified technique as described by Bradfield. The mean hair bulb diameter in children with overt nephrotic syndrome was statistically smaller than the controls. The distributions of hair root morphology amongst them were also statistically different from those of the control group. The hair roots of the children with remission or with questionable relapse were not different from the control group. The application of hair root examination, therefore may be useful in the differentiation of various stages of the nephrotic syndrome.


The vitamin B1, B2 and B6 status of school children in two resettlement areas in Northeast Thailand. The vitamin B1, B2 and B6 status of school children were studied in the Khon Kaen resettlement and irrigation area and in the Lam-takong settlement in northease Thailand using the in vitro tests based on the erythrocyte transketolase, glutathione reductase and glutamate-oxaloacetate transaminase activities. Healthy school children from the Khon Kaen University School were selected as a reference group. The results demonstrate that the vitamin B1 status in the resettlement area is sufficient, but about 20% to 35% of all the children show evidence of vitamin B2 and B6 deficiencies. It is noticed that besides a high prevalence of parasitic infections and poor hygienic conditions the protein and vitamin intake is low and improvement of the situation is necessary.


Socio-economic, health and nutritional status of the villagers in the Nong Wai irrigation area, Khon Kaen, Northeast Thailand. Studies were carried out from June 1974 to May 1975 on the socio-economic status, health and nutritional status of the people in 4 villages, in the irrigation area of the Nong Wai Pioneer Agricultural Project of Khon Kaen Province, Northeast Thailand. The result obtained were compared with those in 2 non-irrigated villages in the same province, in order to identify the health and nutritional problems which might arise during the water resource development in the irrigation area. It was found that in the irrigated villages 90% of the peoples were farmers, while in the non-irrigated villages all were farmers. The socio-economic status of the people in the irrigated villages was much better than those in the non-irrigated ones. The income per family in the former was about three times greater than that in the latter. In the study of the health conditions of the villagers, the vulnerable age group including pre-school children under 7 years of age and school children in the elementary school class 1 and class 2, aged 7-9 years old, served as subjects for investigation. Haematological and physical examinations revealed many children with mild to moderate anaemia, vitamin B2 deficiency and a few cases of hepatomegaly. Anaemic children were found to be more prevalent in the non-irrigated villages than in the irrigated area. The overall parasitic infection rates in children in the irrigated and non-irrigated villages were similar with respect to severity of the infection. Hookworm infection, opisthorchiasis, strongyloidiasis and giardiasis were the leading parasitic infections, while amoebiasis was rare. Ascariasis and trichuriasis were not found. However, the first two helminthic infections had a low grade of intensity. The nutritional status of pre-school children, showed that there were more children with good growth in the irrigated villages than in the non-irrigated one. Serum proteins, albumin and globulin, and urinary urea nitrogen-creatinine ratio revealed normal findings indicating that the children had sufficient protein intake. The results of the urinary hydroxyproline-creatinine index suggested that many of the children in both groups of the villages were at marginal malnutrition status. Surveys on domestic animals including cattle, buffaloes, pigs, and field rats revealed no important zoonotic diseases except leptospirosis in a few rats. Some fish were found to harbour metacercariae of Opisthorchis viverrini, while some snails were positive for cercariae of O. viverrini, Schistosoma spindale, and Echinostoma malayanum. The overall findings indicated that the water resource development by establishing better irrigation, resulted in an improved socio-economic and nutritional status among the villagers, but health conditions and associated parasitic diseases and some nutritional deficiency still existed in the children. However, the findings from this study provide only preliminary data concerning the socio-economic status, health, and nutritional status of the villagers in the irrigation area...


Carcinoma of the thyroid gland, adenoma of the adrenal cortex and peptic ulcer: an unreported association. A 39-year-old man, operated on for duodenal ulcer, was found to have a papillary carcinoma of the thyroid, an aldosterone-producing adenoma of the adrenal cortex, and a recurrence of a peptic ulcer. The probable coincidental occurrence of these diseases in this patient is suggested. Nevertheless, careful investigation of the other endocrine glands in patients with endocrine tumors is recommended.


Conflicts in ethical problems of patient education: strategies for hypertension control explore contractual approach. Experiences in the training of health education interviewers for an intervention strategy in a study which utilized health education strategies for control of hypertension afforded the opportunity for examining the relationship of research to practice and for addressing a recurring concern of health educators in practice, i.e., concern over the ethics of adopting a directing role with patients. This concern, which results in ambivalence in presentation and extreme postures of authoritativeness or passivity as educators, detracts from the potential of a health education intervention. While not evaluated comparatively with other strategies as to outcome, one method of addressing this problem, namely explication of the contractual approach in health education, was utilized informally and has implications for health education interventions. This approach utilizes the patient as a truly active partner and sharpens the use of the educational diagnosis. The outcome has potential positives for patients in personal growth and for educators in the sharpening of skills and in more effective use of their resources. These observations and the ensuing discussions come as an unplanned output of the study from which they derived. However, a variety of experiences in health education lend weight to the impression that the concerns addressed are not atypical of universal concerns among practitioners. Such conclusions suggest the timeliness of testing out the approach in an experimental fashion in an effort to document its use as technique as well as its effectiveness in ultimate outcome.


Effect of prednisolone on the glycosaminoglycan components of the regenerating articular cartilage. Investigations were performed on the effect of prednisolone (0.5 mg/kg) on the regenerating femoral articular cartilage of the knee joint in dogs that had been subjected to semiarthroplasty. After 70 days of prednisolone treatment the dogs were killed and the regenerating articular cartilage was removed, minced, and dried with acetone. The acetone-dried material was used for the determination of galactosamine, glucosamine, uronic acid, sulphate, sialic acid and hydroxyproline. Prednisolone treatment elicited a quantitative increase in galactosamine (30.2%), uronic acid (76.2%), and sulphate (9.1%), while no difference was observed in sialic acid content between the treated and untreated groups. From the molar ratio of the measured components it appears that prednisolone produced an increase in chondroitin sulphate and hyaluronic acid, and a decrease in the keratosulphate content of cartilage. By comparing the values measured in the regenerating articular cartilage of control and prednisolone-treated dogs with the values obtained in the mature articular cartilage, we may conclude that prednisolone--at least as regards the glycosaminoglycans of the ground substance--exerts an accelerating effect on cartilage regeneration.


The hypophysis of the marine teleost fish, Mugil auratus Risso. Owing to its lack of a hypophysial stalk, the hypophysis of the marine fish, Mugil auratus, is of the platybasic type. Its differentiation into adenohypophysial and neurohypophysial regions well conforms with the situation already recognized in other fishes. But, although the adenohypophysis shows distinction into pro-, meso- and meta-adenophypophysis, the lineo-vertical arrangement which they assume is not of common occurrence. By contrast, the neurohypophysis forms the usual central nervous core, surrounded by the adenohypophysial regions. The acidophils constituting the pro-adenohypophysis, having a deep staining affinity, resemble those in the meso-adenohypophysial region. The acidophils of the meso-adenohypophysis occupy a small region, whereas their associating cyanophils occupy a larger ventral region. The meta-adenohypophysis consists of an integral convoluted sac of epithelial amphiphilic cells. Such encloses the bulk of the neurohypophysis. It is remarkable that the neurohypophysial fibres never interdigitate among the meta-adenohypophysial cells, so they are more closely related in arrangement to tetrapods than to fishes.


The hypothalamic neurosecretory system of the marine teleost fish, Mugil auratus risso. The hypothalamic neurosecretory system of the marinefish, Mugil auratus, consists of two nuclei, viz., the nucleus praeopticus and the nucleus laterlis tuberis. Both are paired, and while those of the nucleus praeopticus are vertically arranged as L-shaped bodies, their strand-like counterparts in the nucleus lateralis tuberis extend in an antero-posterior direction. The two constituent bodies of the nucleus praeopticus lie on both sides of the third cerebral ventricle. Each is differentiated into a dorsal pars magnocellularis and a ventral pars parvocellularis. A nervous tract, the hypothalamo-hypophysial tract, extends posteriorly from each body, but it is not until after they penetrate the pituitary gland that they fuse into one structure, the neurohypophysis. Many neurosecretory granules accumulate in the neurohypophysis adjacent to the meta-adenohypophysial region, and fewer scattered granules of varying sizes are also present along the hypothalamo-hypophysial tracts. Inner to these hypothalamo-hypophysial tracts extend the two bodies of the nucleus lateralis tuberis along the infundibular region. Axons from this nucleus extend sideways, and as they merge with those adjacently disposed of the hypothalamo-hypophysial tracts, they enter the pituitary gland as a unified structure.


Electron microscopic autoradiography of serotonin uptake in the ganglia of the fresh-water mussel (Anodonta cygneak L.). After in vitro incubation, the uptake of labelled serotonin was investigated by electron microscopic autoradiography in the ganglia of fresh-water mussel (Anodonta cygnea L.) The labelled serotonin was primarily taken up by the axons of the neurons. The silver grains could always be localized over axons containing eccentric dense-core vesicles with a diameter of 100--200 nm. The results suggest (a) the possibility of the electron microscopic identification of serotonin-containing neurons, and (b) the direct role of the eccentric dense-core vesicles in the storage of serotonin.


Detection of fetal life and growth by means of ultrasonic A-scan. The results achieved in obstetrics by the application of ultrasonic A-scan technique are described. By means of the method fetal life and, from the rate of growth of the biparietal diameter, fetal development were determined in normal and pathological pregnancies.


Effect of absorbable cellulose on the renal parenchyma. Both kidneys of 12 dogs were injured and the wounds were covered with Surgicel which was fixed by means of adhesive. The results were checked by visual inspection and histological tests. The method seems to be suitable for use in appropriate human cases.


Determinantion of testosterone concentration in semen of men with normal or subnormal sperm counts and after vasectomy. Semen from 58 male subjects, aged 22 to 50, was assayed on an individual basis to determine whether T was present in it. Of the subjects examined 23 were normospermic, 14 oligospermic and 9 azoospermic; 12 men had undergone vasectomy were also included in the study. In 39 of the subjects plasma testosterone was estimated. A competitive protein binding technique was employed for T assays while dried extracts of semen were examined by combined gas-chromatography-mass spectrometry and mass fragmentography. Measurable amounts of T were detected in all seminal specimens assayed. This was confirmed by gas chromatography-mass spectrometry which showed a spectrum suggestive of T. The ratio of unconjugated to conjugated steroid in semen was found to be approximately 1:10. Levels of unconjgated T were similar to those found in plasma of normally menstruating women. The mean seminal concentration of unconjugated T (+/-SD) in the specimens assayed was 0.71 ng/ml+/-0.08 for the normospermic, 0.79+/-0.14 for the ezoospermic, 0.69+/-0.09 for the oligospermic, but only 0.38+/-0.04 for the vasectomized subjects. Plasma levels for this androgen were within the range found in normal men of comparable age.  Significant correlation between plasma and seminal T concentration could not be demonstrated and there was no correlation between either of the above parameters and the seminal volume, the number, abnormal form percentage and the motility of spermatozooa in the normo--or oligospermic group. However, when the two groups were pooled into one, significant correlations were found between plasma, (but not seminal T concentration) and the seminal characters examined, perhaps suggesting the number of specimens from the groups should be increased to obtain valid data. Administration of human chorionic gonadotropin produced a marked plasma response as well as a rise of seminal T levels in 3 normospermic subjects whereas cyproterone acetate caused reduction of plasm T levels but had no consistent effect on the seminal concentration of ts steroid although the sensitivity of the seminal method may not have detected smaller changes at this level. The semen from 58 subjects aged 22-50 years was investigated to determine the presence of testosterone (T) in the sperm.  23 of the men were normospermic, 9 azoospermic, 14 oligospermic, and 12 had undergone vasectomy.  Semen was obtained by masturbation, and blood was drawn in 39 men.  A technique using separation by Sephadex LH 20 column chromatography and competitive protein binding was used for T determination.  Measurable amounts of unconjugated T were found in all sepcimens;  and when both the unconjugated and the conjugated fraction of T were estimated, the ratio was 1:10.  The mean seminal concentration of unconjugated T was .71 ng/ml + or -.08 for the normospermic, .79 + or -.14 for the azoospermic, .69 + or -.09 for the oligospermic, and .38 + or -.04 for the vasectomized men.  There was a lack of correlation between plasma and seminal T concentration and the seminal volume, the number, abnormal percentage, and motility of spermatozoa in the normospermic or oligospermic group.


Protein content of human seminal plasma and spermatozoa in relation to sperm counts. Protein concentrations of seminal plasma and spermatozoa were estimated in human normospermic, oligospermic and azoospermic semens. The protein content of seminal plasma ranged from 20 to 60 mg per ml semen and was found to be unrelated to sperm counts. Suspended sediments of azoospermic specimens were found to contain on the average 570+/-86 microng protein per ml semen. This value is about four times higher than in severe oligospermic specimens (0.2 X 10(6) -6.5 X 10(6) cells per ml semen). It is suggested that in azoospermic disorders seminiferous tubules secrete abnormally high amounts of proteinacous material which cannot be eliminated by washings. In addition, destruction of immature cells may contribute to increased protein conten in these specimens. Protein determinations in washed spermatozoa showed a negative relationship between the amount of protein calculated per 10(6) cells and original sperm counts. This trend demonstrates an altered protein metabolism in the spermatozoa of oligospermic specimens which might be responsible for fertility incompetence.


Complex of D-glyceraldehyde-3-phosphate dehydrogenase with Cu2+ ion. I. The apoenzyme-Cu complex. D-Glyceraldehyde-3-phosphate dehydrogenase binds one Cu2+ ion per subunit, which results in the formation of a specific metal-protein complex. This complex exhibits a sharp absorption band around 370 nm, and a broad, small absorption band in the 600-700 nm region. The shape of the absorption spectrum of Cu-GAPD complex in the visible range depends on the anionic composition of the solution. The Cu-GAPD complex is stable in solutions containing phosphate or pyrophosphate anions, but undergoes a slow change in sulfate-, and a rapid change in chloride-containing solutions. The Cys-149 residue of the enzyme is essential for the formation of the Cu-GAPD complex. The sharp absorption at 370 nm presumably corresponds to a charge transfer interaction between the sulfur and the metal ion. Similar absorption bands are shown by the Cu-complexes of papain and thiol-alcalase enzymes. It is assumed that in addition to the reactive thiol groups an imidazole residue in the active site of these enzymes is also involved in the complex formation, and the specific Cu-GAPD Cu-papain and Cu-thiol-alcalase complexes contain a Cys-Cu-His chelate structure.


Different scientifical orientations in approaching so-called schizophrenics. The literature on the phenomenon of "schizophrenia" presents different scientific orientations. These are classified under five headings: biophysical, intrapsychic, phenomenological, behavioural and socio-cultural. This classification corresponds to the different contemporary professional orientations. However, each orientation provides only the interpretation of one aspect of the total phenomenon studied. Moreover, most interpretations are still imperfectly developed. A comprehensive transdimensional approach is a task for the future.