The ameloblast movement in rat incisor. L.M., S.E.M. and C.L.S.M. study

The internal epithelium of enamel organ and the below enamel surface during growth of the lower incisor, were examinated in ten Wistar rat 12-27 weeks old and weighing between 150/200 gr, by means of immuno histochemical, light and scanning electron microscopy techniques. Our specimens indicate that during the outer enamel secretion the anti-actin positivity goes from distal terminal web to infra nuclear region of cell body. The results of the present study do not support the active movement hypothesis, conversely they support the Warshawsky (1992) hypothesis, i.e. the distal terminal web permits the maintenance and the assembling of ameloblasts during enamel growth. Hence we do agree with Osborn (1970) who reported that, during secretion, ameloblasts move passively in response to secretory forces.     

Changes of the e.e.g. during a c.n.v. paradigm

An experimental set-up and a method of analysis are described which permit the performance of e.e.g. analysis under contingent negative variation (c.n.v.) conditions with repeated stimulation. Investigations of six subjects showed a significant reduction in the average power in the alpha band immediately after the imperative stimulus, which lasted only about 1 second. In the interstimulus interval during the c.n.v. a less marked power reduction could be observed. Since the reduction of the average power in the alpha band was approximately the same for both hemispheres and since it was also dependent on the modality of the stimulus, an interrelation-ship is assumed between the directed attention and the reduction observed. This appears to allow the possibility of objectively analysing cortical functions by means of an analysis of scalp recordings under c.n.v. conditions.     

Avian tibial dyschondroplasia. I. Ultrastructure.

Tibial dyschondroplasia is an abnormality of the growth cartilage that occurs in chickens and other rapidly growing animals. The disease is characterized by a mass of avascular opaque cartilage, which is continuous with the growth plate of the proximal tibia and extends into the metaphysis. In this study electron micrographs revealed that chondrocytes in the hypertrophic zone of the growth plate were normal in appearance with the exception that the cells did not undergo complete hypertrophy. In the proximal region of the lesion, cells began to undergo necrotic changes suggestive of an energy depletion. These changes included dilatation and vesiculation of the endoplasmic reticulum, enlargement of the paranuclear space, mitochondrial swelling with dilatation of the intracristal spaces and the appearance of electron-dense, flocculent material in the mitochondrial matrix, chromatin margination, and dilatation of the Golgi saccules. Chondrocytes also occurred with rarefied cytoplasm and atrophic Golgi saccules. A few cartilage cells in the proximal region of smaller lesions contained crescentic caps of condensed chromatin in the nuclei, which is indicative of apoptosis. These cells also exhibited dilated endoplasmic reticulum and lamellar bodies; and sometimes, in the proximal region of the lesion, they appeared to be condensed and convoluted. This process continued in the mid and distal regions. The condensed necrotic cells appeared as amorphous osmiophilic masses with karyorrhexic and pyknotic nuclei. Matrix vesicles were observed at all levels of the lesion, but calcified only at the distal edge of the lesion, where mineralization of both matrix and cells occurred. The resulting shell of mineral may act as a diffusion barrier.     

Antithrombin III. Theory and clinical applications. H. P. Smith Memorial Lecture.

Antithrombin III is one of the main inhibitors in the blood coagulation mechanisms. Thrombin and factor Xa are slowly inactivated by it, as well as other serine proteinases of the coagulation mechanisms. Heparin tremendously accelerates the inhibitory function of antithrombin III. In the process antithrombin III activity is also reduced. Heparin retards the thrombin-fibrinogen reaction, but otherwise the effectiveness of heparin as an anticoagulant depends on antithrombin III in laboratory experiments, as well as in therapeutics. The activation of prothrombin is inhibited, and any thrombin or other vulnerable protease that might generate becomes inactivated. The measurement of antithrombin III concentration in blood is now achieved by research methods, as well as by methods that are practical for routine use. The tests require either thrombin or factor Xa as substrate, and could be specific for antithrombin III. There are congenital as well as acquired deficiencies of antithrombin III. The inhibitor is also found in tissues.     

Neonatal thymus grafts. II. Cellular events.

Neonatal thymus undergoes sequential necrosis and cell regeneration after grafting under the kidney capsule in normal and thymectomized recipients. This regeneration assessed in terms of cell number, response to mitogens, in vivo steroid sensitivity, level of antigen-binding cells, and cellular distribution on Ficoll gradient is not influenced by the presence of host thymus or by FTS injections. The grafted thymus shows a similar pattern of development as control thymus of the same age followed up in situ, with the exception of age-related involution the onset of which takes place earlier in the grafted thymus.     

The Ph.D. to M.D. program: the seven-year mark.

The Ph.D. to M.D. Program, a two-year, accelerated medical curriculum for Ph.D. scientists, has been in operation at the University of Miami for over seven years. Two hundred and nine students from a broad range of scientific disciplines have been admitted, and attrition has been remarkably low (less than 1 per cent). One hundred and thirty-five of the entering candidates (65 per cent) were nonbiologists, but their achievements in the curriculum were virtually equivalent to those of their biologically oriented peers. All graduates have commenced house-staff training, the vast majority at university or university-affiliated hospitals. Of the 46 graduates who have completed some aspect of postgraduate training, 22 are in private practice, 20 are in teaching and research positions and four are scientific administrators in industry. The record indicates that through intensive medical education, the program is able to bring a group of scientists with unusual talents to the theory and practice of medicine.     

Prevention of E.N.T. diseases

World Health Organization has announced 'HEALTH FOR ALL BY YEAR 2000'. Unfortunately the emphasis at present is only on early diagnosis of a disease and its treatment. The modern investigations and treatment has become very costly which a poor man cannot afford. Preventive medicine is less costly. The developing countries have many socio-economic problems of population explosion, poverty, ignorance, illiteracy, shifting of population from rural to urban areas for employment and traffic jams in cities. Rapid industrialization has resulted in indiscriminate cutting of trees and forests and increasing pollution. Under the present circumstances one wonders whether it would be possible to achieve the WHO's object of health for all or will it remain a dream! The role of 'Yoga and Meditation' and vegetarian diet has been recognised world over for maintenance of normal physical and mental health; these help to lessen mental tension in the present competitive world full of stress and strain for all of us. 3-4% of people in the world avail the beneficial effects of alternative system of medicine is complete as each has its own merits and limitations. Hence our aim should be to choose an integrated system of medicine which would help in preventing diseases and treat them early by a safe and effective procedure. In the present political situation in our country none of the parties have announced any definite programme for population control, through it is a grave problem. We will not be able to fulfil our object of reaching our target of Health for all without strict population control major. Unless this programme is undertaken seriously as a priority in a co-ordinated disciplined manner by all of us and completed in a given period of time, the younger generation will not forgive us. We hope that as true citizens of India we will not spare any efforts on our part in attaining this objective for a bright future.     

Penicillamine and hydroxychloroquine in the treatment of severe juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind placebo-controlled trial

One hundred sixty-two children with severe juvenile rheumatoid arthritis were entered in a randomized, double-blind, placebo-controlled 12-month clinical trial designed to establish the efficacy and safety of two slower-acting antirheumatic drugs, penicillamine and hydroxychloroquine. The study was a cooperative effort of the United States and the Soviet Union. One group of subjects received 10 mg of penicillamine per kilogram of body weight per day, another group received 6 mg of hydroxychloroquine per kilogram daily, and a third group received placebo. All three groups were allowed a single concurrent nonsteroidal antiinflammatory drug, but no other antirheumatic medications, including corticosteroids. All three groups had dramatic improvement in many of the clinical and laboratory outcome variables after one year of study. There were no significant differences in efficacy between the penicillamine and placebo groups. Pain on movement was the only index of articular disease that was alleviated more by hydroxychloroquine than by placebo. Serious adverse drug reactions attributable to the active agents were rare. We were unable to demonstrate that, in the presence of a nonsteroidal antiinflammatory drug, either penicillamine or hydroxychloroquine is superior to placebo in the treatment of children with juvenile rheumatoid arthritis.     

Analysis of pairs of individual Ia-E.P.S.P.S in single motoneurones.

1. Recordings of individual e.p.s.p.s evoked by the action of single medial gastrocnemius Ia fibres have been made from medial gastrocnemius motoneurones. In many motoneurones the action of two Ia fibres has been observed and the properties of the e.p.s.p.s compared. 2. For sixty-three pairs of averaged e.p.s.p.s, each from the same motoneurone, the ratio of half-widths was plotted against the ratio of rise times. These results were compared with theoretical values derived from the Rall compartmental model. It was found that variations in synaptic current time courses and differences in the termination of localized synaptic terminals were not sufficient to account for all the data. 3. Amplitude and rise time were inversely related but the correlation coefficient was very low. For pairs of e.p.s.p.s in the same motoneurone the e.p.s.p. with the fast rise time was larger than that with the slow rise time in forty-eight of sixty-three cases. 4. In a given motoneurone individual e.p.s.p.s evoked by the action of different Ia fibres did not vary greatly in amplitude. The ratio of peak amplitudes was less than 3 for 86% of the pairs of e.p.s.p.s examined, and the maximum was 4-8. 5. Amplitude histograms were constructed for individual e.p.s.p.s at thirty-three synapses. Twenty-two of them could be shown to satisfy the Poisson law. The others satisfied the binomial law or neither. 6. Within a given motoneurone the amplitude of an e.p.s.p. is closely related to the mean number of quanta released but not to the amplitude of the unit e.p.s.p. produced by the action of a single quantum of transmitter.     

Gelchromatographie. 9. Mitt.: Polymethacrylatgele1

The influence of the conditions of synthesis on gelchromatographic properties of copoly-(methyl methacrylate) gels crosslinked with glycol dimethacrylate is described. Homogeneously crosslinking polymerization leads to gels with excluded molecular weights up to about 6000. Copolymerization in presence of inert compounds results in heterogeneous structures. By heterogeneously crosslinking copolymerization gels are obtainable with formal excluded molecular weights higher than 10¹⁰. Variation of the amount of crosslinking agent and the solvent power of the inert compound allows to fit the excluded molecular weight of the gels to any separation problem. The polymerization of dimethacrylates of poly(ethylenoxides) results in hydrophilic gels without hydroxyl groups. These gels are suitable for separation in water and in organic solvents.     

Avian tibial dyschondroplasia. III. Electron probe analysis.

Tibial dyschondroplastic (TD) lesions and their associated growth plates, obtained from chickens, were prepared by freeze-drying and embedding in an anhydrous epoxy resin. Quantitative electron probe analysis was performed on dry, unstained sections. Levels of Na, Mg, P, S, Cl, K, and Ca were determined in cytoplasm (endoplasmic reticulum), mitochondria, and extracellular matrix of the proliferative, prehypertrophic, and early hypertrophic zones of the growth plate and in the proximal, mid, and distal regions of the lesion. A zone of calcification in the growth plate was absent. The concentration of elements in all regions of the TD growth plate was the same as found in an earlier study for normal growth plate. The cytoplasm of proximal lesion chondrocytes was similar to that of early hypertrophic chondrocytes. However, in the remainder of the lesion there was a progressive increase in cellular Na, S, Cl, and Ca and a progressive loss of P. In matrix, there was less S and K than expected in all regions of growth plate and lesion, except in the proliferating zone. Also, in matrix of the distal lesion there was less Na and Cl. The levels of Na, S, Cl, and K in matrix may have been lowered by their adsorption into the condensed masses of dead cells. Mitochondria acquire only half as much Ca and P as normal and release it earlier than usual (ie, early prehypertrophic cells, rather than chondrocytes of the lower hypertrophic zone). There were no granules in mitochondria of the cells at all levels of the lesion, even though anhydrous methods were used. The first sign of the disease appears in the matrix of the growth plate, where it seems that S and K are in abnormally low amounts. Although there are sufficient levels of Ca and P present, the matrix does not calcify. The cartilage remains avascular, and the cells appear to be dying. The event that triggers the chondrocytes of the growth plate to form an abnormal uncalcified matrix is not known.     

The Jefferson-Penn State B.S.-M.D. program: a 26-year experience.

Since the 1960s a number of physicians have completed both their baccalaureate and their M.D. degrees in six or fewer years. In this longitudinal study the authors track the academic performances, clinical ratings, and career follow-up data of 659 students in one of these accelerated programs, the Jefferson Medical College-Pennsylvania State University B.S.-M.D. program, from entering years 1964 through 1989. The medical school performances, clinical performances in residencies, and rates of board certification and faculty appointment of the accelerated students compared favorably with those of a control group of medical students with similar high school credentials who had followed a four-year baccalaureate program. The authors conclude that a carefully chosen group of students can achieve high academic standards in an accelerated medical school program, graduate as younger physicians able to perform well in postgraduate training, and go on to highly productive careers in medicine.     

Application of catheter-tip i.s.f.e.t. for continuousin vivo measurement

A catheter-tip pH sensor was developed for possible clinical and biomedical application, using an ion-sensitive field-effect transistor (i.s.f.e.t.). Its signal drift in buffer solutions during continuous measurement was less than 3 mV in 24 h (equivalent to about 0·05 pH in 24 h). The electric insulation was perfect when soaked in buffer solutions for more than 3 months. A continuousin vivo pH measurement was successfully achieved in nonheparinised arterial blood of a japanese monkey. There was no significant sign of clot formation for 8 hours. It revealed quick responses to respiratory acidosis and alkalosis, and the observed pH values were in accordance with those confirmed by a blood pH analyser. Also, a catheter-tip pCO₂ sensor was prepared, using the catheter-tip pH i.s.f.e.t. The response time was 2 min for a 90% change in CO₂ tension. The muscle pCO₂ monitoring tested with it indicated a similar result to those with medical mass spectrometer.     

Magnesium and blood pressure. II. Clinical studies.

Magnesium deficit may be considered as a cardiovascular risk because of its aetiopathogenic role in the genesis of atherogenous dyslipidaemias and the so-called "idiopathic" mitral valve prolapse. It does not, however, constitute a major antihypertensive factor, though it may sometimes be an accessory co-factor. Plasma magnesium is generally normal in untreated hypertensive patients and normotension is the rule during magnesium deficit. An inverse relationship between magnesium and renin in the plasma of hypertensives has not been confirmed. In practice, plasma magnesium seems to be related to the evolution of the disease. An inverse correlation between blood pressure and erythrocyte total and free magnesium levels has been observed in diverse selected populations but no adjustment has been made in these studies for important covariables. A weak positive association between blood pressure and erythrocyte free magnesium was lost in a multivariate regression analysis. As a rule there is no difference between erythrocyte, leucocyte, and lymphocyte magnesium in hypertensives and controls. More often no relation between urinary magnesium and blood pressure is observed. Daily urine magnesium may be increased with increased excretion of urine adrenaline. Epidemiological data on dietary magnesium, particularly in drinking water, should be carefully scrutinized: these studies do not establish a major role for magnesium as an antihypertensive factor but confirm the importance of magnesium deficit as a nephrocardiovascular risk factor and sometimes gives support for a role of magnesium as an antihypertensive cofactor. The use of magnesium-depleting drugs in hypertensive patients may induce magnesium depletion which must be palliated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lectin-dependent neutrophil-mediated cytotoxicity. I. Characteristics.

Isolated normal human peripheral neutrophils became cytotoxic to chicken red blood cells (CRBC) in the presence of phytohaemagglutinin (PHA) and concanavalin A (Con A), a phenomenon which we have termed lectin-dependent neutrophilmediated cytotoxicity (LDNMC). Substantial cytotoxicity could be demonstrated by 1 h of incubation at 37 degrees. Isolated human peripheral lymphocytes were not cytotoxic to CRBC in the presence of these lectins, even after 18 h of incubation. Both PHA and Con A exhibited dose responses over a wide concentration range and displayed progressive, time-dependent cytotoxicity. Cytotoxicity for both PHA and Con A was greater at 37 degrees than at 22 degrees, and was undetectable at 4 degrees. CRBC as target cells were much more readily lysed than either sheep or human erythrocytes. Erythrophagocytosis did not appear to play a role.     

Avian tibial dyschondroplasia. II. Biochemical changes.

Biochemical parameters (dry matter, DNA, protein, cAMP, and calmodulin) were measured in tibial dyschondroplastic (TD) cartilage. This abnormal cartilage, which is a mass of unmineralized, unvascularized cartilage found in the proximal metaphysis of the tibiotarsus and tarsometatarsus, was compared with normal epiphyseal growth plate and hypertrophic cartilage obtained from day-old embryonic cone. The latter tissue is an example of cartilage which rapidly undergoes vascularization and mineralization. When compared with normal growth plate, tibial dyschondroplastic cartilage was found to contain lower amounts of dry matter, DNA, protein, cAMP, and calmodulin. This cartilage did not respond to factors in serum which stimulate 35S uptake. Although the above two types of cartilage contained similar amounts of ash, TD cartilage had less phosphorus and potassium and more sodium than the growth plate. The two types of cartilage had similar lysozyme activity and proteoglycan (hexosamine) content. In many of the parameters measured, day-old hypertrophic cartilage was similar to the normal growth plate. However, these tissues did differ in DNA, protein, ash, and lysozyme content. Substantially greater amounts of ash and lysozyme were found in the hypertrophic cartilage, which appeared to be related to events of mineralization and vascularization of this cartilage. These events did not occur in the abnormal cartilage cells found in the tibial dyschondroplastic lesion.     

Lindon J. Eaves,Ph.D., M.A. (Oxon), D.Sc. Theory-Model-Data

We begin this special issue by providing a glimpse into the career of Dr. Lindon J. Eaves, from the perspectives of a student, postdoc, instructor, assistant to associate and full professor over the last 20 odd years. We focus primarily on Lindon’s contributions to methodological issues and research designs to address them, in particular those related to models for extended twin-family designs, for the development of adolescent behavior, for genotype-environment covariation and interaction, and their application to the Virginia 30,000 and the Virginia Twin Study of Adolescent Behavioral Development. We then introduce the collection of papers in this special festschrift issue of Behavior Genetics, celebrating Dr. Eaves achievements over the last 40 years.     

Alaskan malamute chondrodysplasia. I. Bone composition studies.

Chondrodysplastic Alaskan Malamutes exhibit concentrations of calcium, phosphorus and magnesium in radius, ulna, and humerus bone segments similar to those of non-chondrodysplastic dogs of similar age. Significant differences in extractability of mineral components with 5% EDTA were observed in specific bone segments. Although these data suggest that a primary derangement in calcium and phosphorus was possible the magnitude of the differences strongly suggested it unlikely and stress or mechanical factors may account for some of the observed differences. The possibility that chondrodysplasia provides a model for human disorders such as fibrogenesis imperfecta ossium was discussed. These data presented support a previous hypothesis that the chondrodysplasia is not a vitamin D-resistant rickets syndrome.     

Natural selection associated with birth weight. IV. U.S.A. data from 1950 to 1976

Differential still birth rates as a function of birth weight have been studied in all single births in the United States of America (White and Non-white groups) in the years 1950, 1958, 1967 and 1976. During the 26-year interval a reduction of both the stabilizing effect and the intensity of selection have been observed. For the 1960 cohort it has been found that selection associated with birth weight is mainly operating in the perinatal period and only minor effects are still present at one year of age.