[Histological and biochemical studies on the postnatal development of the guinea pig liver (author's transl)]. In newborn guinea pigs the structural development of the liver was studied with emphasis on changes in the lipid content as related to biochemical parameters. The livers of 149 guinea pigs (strain PIRBRIGHT) up to an age of 21 days were examined. The mothers were grouped in cages and kept as usual (room temperature 22 degrees C, air humidity 60-70%, natural light-dark rhythm and commercial standard diet ad libitum, sawdust and straw as bedding). Pregnant animals were placed in individual cages being left there together with their offspring until weaning or sacrification. In this period additional uptake of solid diet was allowed to the guinea pigs. The animals were bleeded to death in anesthesia (by head stroke). For histological examination tissue samples from the Lobes sinister lateralis were fixed in Barker's formol or absolute alcohol. The following staining reactions were applied (paraffin embedding or frozen sections): haemalum-eosin stain; PAS-reaction; Sudan III; Sudan black; Best's carmine (for details on the techniques see ROMEIS 1968). In biochemical analysis the total lipids of the liver were determined by the isolation methods reported by FOLCH et al.(1957). Moreover, in modification of the analytical procedures earlier described (SALLMANN 1972 a, b) several fractions of the liver total lipids could be isolated. By dialysis against a rubber membrane a dialysable lipid component (hydrocarbons, triglycerides, incomplete glycerides, cholesterol and free lipid acids) was isolated from the phosphatide fractions. Further separation of the "dialysable" lipids on Florisil columns yielded purified glyceride fractions. The total lipids as well as all components isolated from these were determined gravimetrically after removal of the solvents concerned. In biochemical analysis the livers of fetuses 10-12 days ante partum and of young animals up to 53 days were included. Results (see also table 1): The relative liver weight--related to the body weight reduced for that of the gastrointestinal tract--is highest at birth. It is lowered independent of the development of the gastrointestinal tract within a short period, then it remains fairly constant during the rest of the time of observation. On the 1st day abundant lipids are regularly distributed throughout the whole liver lobule (fig. 1). Beginning with the 3rd day the central parts of the lobules are nearly free from lipids, only in the peripheral zones of the lobules lipid augmentation was still observed. Consequently the marked decrease in liver weight is due to the rapid reduction of lipids within the first 3 days of life. These observations are in accordance with the biochemical findings: about 10 days ante partum noticeable storage of lipids occurs in the liver reaching its peak 2 to 3 days after birth (physiological fatty infiltration of the liver during the last days of intrauterine life). In fetal liver tissue predominantly tryglycerides are augmented.


Inverse localization of Ca2+ and La3+ high affinity binding sites of the red cell membrane. Glutaraldehyde fixation in the presence of both 90 mM La3+ resulted in opaque deposits were also seen in specimens fixed in a glutaraldehyde-CaCl2 medium devoid of La3+. In that case only small amounts of a moderately opaque substance had accumulated or remained at the external surface of the erythrocyte membrane. Specimens previously fixed with Ca2+, La3+ supplemented glutaraldehyde lost their internal deposits completely during postifixation with OsO4. The findings provide evidence of Ca2+ high affinity binding sites at the internal surface of the erythrocyte membrane presumably identical with the filamentous matrix. Glycocalyx constituents are considered external Ca2+ low affinity binding sites, however, capable of accumulating high amounts of La3+ during glutaraldehyde fixation.


Effects of kidney extract on the folic acid induced proliferation of the rat kidney. Single injection of a high dose of folic acid causes a proliferation of the kidney with an increase of the 3H-thymidine incorporation into the DNA of kidney cortex slices in rats. An aqueous extract from rat kidneys inhibits the increase of 3H-thymidine incorporation. The inhibition begins after 4 hours. The maximum effect is observed between 11 and 17 hours after injection of the kidney extract. The kidney extract also inhibits the increase of the DNA content per kidney after folic acid injection. Heart, lung, spleen and liver extracts and bovine serum albumin do not lead to inhibition of the 3H-thymidine incorporation into the DNA of kidney cortex sclices.


Diterpene acids as larval growth inhibitors. Kaurenoic and trachylobanoic acids from sunflower inhibited larval development in several Lepidoptera species. The tricyclic resin acids were also effective in curtailing growth of Pectinophora gossypiella and either reduction to carbinol or esterification of the carboxyl group lowered activity. Partial reversal of growth inhibition in the presence of relatively large amounts of cholesterol suggests an interaction with the insects' hormonal system.


The citrate synthase from Bacillus Stearothermophilus. Citrate synthase has been purified to apparent homogeneity from Bacillus stearothermophilus. Its kinetic and regulatory properties, and molecular weight, are similar to those of the enzymes from suitable mesophilic counterparts, but its thermal stability is considerably greater.


Increased in vitro phosphorylation of rat liver nucleolar proteins following triiodothyronine administration. It has been shown that triiodothyronine (Ta) administration to thyroidectomized rats induces an increase in the in vitro net 32P uptake into liver nucleolar proteins. Such an increase depends on a stimulation of the nucleolus-associated protein kinase activity and not on a lower dephosphorylation rate.


Synthesis of S-lactoyl-glutathione using glyoxalase I bound to sepharose 4B. Glyoxalase I bound to Sepharose 4B was used for synthesis of S-lactoyl-glutathione. The bound enzyme does not lose its activity during several months storing and can be used many times for synthesis of S-lactoyl-glutathione. This reaction product can be used as a substrate for glyoxalase II without any further purification.


Stable lipid peroxidation products in human skin: detection, ultraviolet light-induced increase, pathogenic importance. Products of lipid peroxidation (malonaldehyde, Schiff-bases) were detected in human skin. These products were increased after UV-light exposition, on chronically sun-exposed areas as well as with advancing age. Malonaldehyde cross linked epidermal glucose-6-phosphate-dehydrogenase and diminished their activity.


Macronuclear response of Paramaecium multimicronucleatum to L-lysine. A strain of Paramaecium multimicronucleatum was exposed to a medium containing L-lysine; the concentrations of the amino acid were 0.1%, 0.5% and 1.0% for different sets of experiments. In these two latter concentrations, the macronucleus of the ciliate broke down into innumerable small fragments, the microspheres. The micro-nuclei remained inert. The microspheres left the body of paramaecium as cell-free, self-duplicating entities constituted of DNA and RNA and enveloped by a protein coat. They had no nuclear membrane and they resembled the prokaryotes. Grown in culture medium with 0.1% horse serum, the microspheres transformed into small amoebae having typical eukaryotic features. These amoebae maintained a typical cyst-trophic cycle during the successive sub-cultures; they had no similarity with the paramaecia.


Unusual membrane fracture faces in polymorphonuclear leukocyte granules. Freeze fracturing of azurophil and specific granules from rabbit polymorphonuclear leukocytes reveals unusually high numbers of intramembrane particles. Both granules have significantly higher particle densities on the B than on the A fracture face.


Degranulating activity in hybrid cells derived from rat peritoneal mast cells and ehrlich ascites. Fusion of rat mast cells and Ehrlich ascites tumor cells was mediated by HVJ. Compound 48/80-induced degranulation occurred in the fused cells formed from two mast cells and one tumor cell, but not in the fused cells from one mast cell and two or more tumor cells.


Correlation of blood and brain amino acids in hypoglycemic and normoglycemic rats. Utilization of gluconeogenic amino acids as a source of energy by brain can occur in starved newborn rats. This capacity is lost later in life as evidenced by changing ratios in blood and brain concentrations between fed and fasted animals.


Neurochemical correlates of alloxan diabetes: protein and ribonucleic acid levels in the different regions of the rat brain. The levels of protein and ribonucleic acid in the cerebrum, cerebellum, optic lobes and medulla oblongata of normal and alloxan-diabetic rats were measured. In general, the protein content and levels of ribonucleic acid in the broad compartments of the brain of rat decreased during diabetes.


Cardiac pressoreceptors and peripheral resistance. The results obtained show that the pressoreceptors, probably ubicated in the left ventricle of the rat, respond to the distention with vasodilatation. The afferent tract of this reflex is in the vagus nerve and the efferent one is in the sympathetic nervous system. The probable function of this reflex is discussed.


Hypervascularization of the cerebral cortex in lead-induced encephalopathy. Pregnant rats were fed a diet containing 1.8% lead acetate for 8 days before delivery until the young were 3 month old. The density of the cerebral cortex capillaries of the infant rats and their convolution rate were studied morphometrically and noted to increase significantly according to the duration of lead treatment, as demonstrated by two-way analysis of variance. On the other hand, the thickness of the cortex reduced progressively. The increase of both capillary density and convolution rate is supposed to be related with this involution of cortex. This provides a quantitative insight of the previously described 'capillary activation' phenomenon, caused by lead encephalopathy and reveals it as a significant sequel of saturnine action.


Regional variations of choline-acetyltransferase in the chick embryo optic lobe. The specific activity of CAT and AChE was determined in different regions of the chick embryo optic lobe at several stages of development. Regional differences in CAT activity appeared in 9-day-old tectum, being the posterobasal area the one with higher enzymatic activity. On the other hand, at 6th and 13th day of development, the levels of AChE and CAT are similar throughout the optic lobe.


Dyslexia and specifically distorted drawings of the face - a new subgroup with prosopagnosia-like signs. Identification of a subgroup (38%) of dyslexics (new syndrome?). These, against controls (5.5%), drew 'neolithic' face configurations analogous to those visually experienced in prosop-agnosia. Essential symptoms of this subgroup are seen as result of specific early ways of processing visual data: lexical shapes (letters, words) and facial features, as if these were concrete entities, not abstract component parts. Thus, with letters, taken as entities, d = q, d = b, N = Z.


Experimental coupling of crab (Carcinus maenas) second maxilla neural motor to an alternating current. Movements of the crab gill bailer were entrained to an alternating current applied to the thoracic ganglion. There was little distortion of the muscle recruitment cycle, both absolute and relative coordination were observed, and the phase of the driven system in the driving cycle was a function of the difference between free running and driving frequencies.


Release of renal kallikrein to the perfusate by isolated rat kidney. The addition of furosemide to the fluid used to perfuse isolated rat kidney increases the kallikrein activity found in the perfusion fluid. The experiments favour the concept that furosemide activates a kallikrein precursor or/and the synthesis and release of kallikrein in the kidneys.


Changes in heart rate levels during avoidance conditioning in the rabbit. During avoidance conditioning heart rate levels tend to increase or to decrease according to their initial values and these changes are not related to learning or performance of the task.


[The waxwing Bombycilla garrulus as a frugivorous feeding specialist (author's transl)]. Eight waxwings, Bombycilla garrulus, were fed exclusively with vegetable food for periods of 10-18 days. In contrast to other song birds, they maintained or increased body weight during that time, or reduced it only moderately. Thus the waxwing is a feeding specialist which can subsist at least temporarily on a totally vegetable diet.


Cholinesterase reactivators - contribution to the study of their metabolic effects. Cholinesterase reactivators - trimedoxim, methoxim and obidoxim - injected in the dose of 20 mg/kg s.c., increase muscle glycogen concentration in normal, but not in adrenalectomized rats. This effect may be in connection with simoultaneously found rise of serum corticosteron level. Trimedoxim decreases adrenaline, methoxim and obidoxim noradrenaline concentration in adrenals.


Early investigations on the effect of methyl mercuric chloride upon DMN-acute hepatotoxicity. Acute toxicity induced by DMN was partially prevented by previously administering methyl mercuric chloride (MMC), a chemical inhibitor of the drug metabolizing enzyme system (DMES). We have studied the early changes occurring during the course of DMN-intoxication, namely disaggregation of polysomal profiles and necrosis, evaluated morphologically and by the release of S-GPT.


Mescaline: its effects on learning rate and dopamine metabolism in goldfish (Carassius auratus). The pharmacological action of mescaline on goldfish was studied with the Bitterman-Agranoff shock-avoidance test. In short term experiments with high mescaline doses an increase in learning rates was observed. Similar results were obtained with apomorphine and L-dopa. However, when the fish were exposed to smaller mescaline doses (or to fluphenazine) for 3 days, their ability to avoid electric shock was reduced. Apparently, mescaline induced a release of dopamine which stimulated central dopaminergic systems. Subsequently, MAO destroys the liberated dopamine. Thus, the ensuing dopamine deficit appears to be responsible for the marked changes in behavior in the chronic experiment.


Lamellated sensory nerve endings in guinea-pig adrenals. Lamellated sensory nerve endings were observed in the adrenal gland of guinea-pigs located at the corticomedullary junction close to venous blood vessels. We suggest that they form the afferents of a system contributing to a local regulation of adrenal blood flow.


Failure of 3H-serine to induce radioactivity in presumed glycinergic retinal neurons. 3H-serine does not label retinal neurons selectively when injected intraocularly in rabbits, as would have been expected if it had been converted to neutrotransmitter glycine. The reason is unknown, but one possibility is that the conversion was blocked during the conditions of the experiment.


Penetration of melanocytes from embryonic japanese quail peritoneum into associated embryonic avian gonads, grown on chicken chorioallantoic membrane. After association on chorioallantoic membrane (CAM) of an embryonic bird testis with pigmented peritoneum from a Japanese quail embryo, numerous melanocytes penetrate in its interstitial tissue. If, instead of a testis, an ovary is transplanted under similar conditions, then the melanocytes may be found in the medulla or between the secondary sex cords at the rim of the ovary.


The exotoxin of Bacillus thuringiensis: a new C-mitotic agent. Thuringiensin A, an exotoxin from Bacillus thuringiensis, a constituent of the microbial insectide thuricide has been found to inhibit mitotic spindle, condense and scatter chromosomes. It may therefore be a promizing tool in future cell biological studies.


Mast-cell reaction in precancerous mouse skin: an immunological response? The promotion phase of carcinogenesis in mouse skin is accompanied by a mast-cell reaction in the upper dermis. Evidence is presented which suggests that this may be an immunological response, whereby distant lymphocytes migrate to the area and, in the presence of young fibroblasts, become transformed into tissue mast cells.


The origin of experimental brain tumours: a sequential study. A sequential study of rat brains treated transplacetally with the neurotropic carcinogen ethylnitrosourea reveals small foci of cell proliferations from the age of 8 weeks. These lesions consist mainly of undifferentiated cells of the subependymal plate type. They occur in those areas in which gliomas develop and represent the earliest, histologically detectable, changes in the development of brain tumours.


The effect of two forms of light on the development of the neonatal rat retina. The effects of red and far red light on the development of the retinas were studied in the neonatal rat models. Red light appeared to be stimulatory and far red light appeared to be inhibitory.


Inhibition and stimulation by 5-bromodeoxyuridine of erythropoiesis by chick blood island cells. Erythropoiesis in liquid cultures of cell populations resolved from chick blastodiscs at the primitive streak and head-fold stages was totally inhibited by 5-8 mug/ml of 5-bromodeoxyuridine. However, concentrations of 0.2 mug/ml of the nucleoside enhanced the number of erythroid cells formed.


The abscence of intravascular clotting in rat anaphylaxis. Intravascular fibrin formation could not be detected in various phase of IgE mediated anaphylactic shock of rats, either by using an isotope technique or testing the plasma samples by the ethanol gelation test.


Plasma fibrinogen response in the rat after thyroid stimulating hormone therapy. Thyroid Stimulating Hormone (TSH) increased the levels of plasma fibrinogen in the presence or absence of the thyroid gland. This finding suggests that this hormone produces an elevation of fibrinogen in rats by an extra-thyroideal mechanism.


[Observations on the acceleration of the sexual maturation of female mice by the presence of males and by exogenous oestrogen (author's transl)]. The influence of the presence of adult males on the acceleration of sexual maturation of female mice was examined under various experimental conditions and compared with the influence of exogenous oestrogen. The criteria of sexual maturation were not equally influenced. It is concluded that sexual maturation is a complex feature and that acceleration of single criteria does not signify sexual maturation.


A simple method for blood exchange in mice. Ease of transfusion and high long-term survival rate were obtained when whole blood was administered via the corpus cavernosum of the penis and removed from the orbital sinus of male C57Bl mice. When 2 volumes of blood are replaced approximately 14% of pre-transfusion red cells remain after hematocrit corrections are made. The post-transfusion hematocrit levels dropped 19%, probably the result of leakage, which is difficult to avoid.


A simple algorithm for the solution of the 'n X m' case of a binding equilibrium. Accurate estimates of the equilibrium concentrations in the non-interactive reaction of several ligands with several classes of binding sites with univalent stoichiometry can be rapidly obtained by a simple method of successive approximations on a programmable desk calculator.


[The primary structure of bovine alpha s2 caseins]. The bovine alphas2-, alphas3-, alphas4- and alphas6-caseins [1] were isolated. The 4 proteins had the same amino-acid composition and C-terminal sequence, but different phosphorus contents. From a mixture of these proteins (designated as 'alphas2-complex') and from alphas3-casein a single and identical N-terminal sequence was obtained by Edman degradation. It seems therefore that the 4 proteins have the same peptide chain and only differ in their phosphorus content. For this reason we propose to modify the nomenclature of Annan and Mason [1] and to use in future the single term alphas2 to designate the caseins which have been previously called alphas2,alphas3,alphas4 and alphas6 by these authors. The study of the primary structure of the peptide chain, which has confirmed these results, was undertaken on the S-carboxymethylated alphas2-complex. From a cyanogen bromide digest and from a tryptic hydrolyzate of the alphas2-complex, 5 and 25 peptides were obtained respectively, both sets of peptides accounting for the whole peptide chain. Examination of the tryptic peptides containing methionine combined with the N- and C-terminal sequences of the alphas2-complex and some CNBr peptides, gave the order of the CNBr peptides, H.CN4--CN2--CN5--CN1--CN3.OH, which contain 4, 22, 115, 49 and 17 residues respectively. A partial sequence accounting for half of the peptide chain of the alphas2-complex is given. This peptide chain is likely composed of 207 amino-acid residues.


NIH funding and biomedical publication output. An investigation of the relationship between NIH funding and biomedical publication output is reported for 229 major NIH supported institutions. A correlation of 0.95 was found between the amount of NIH funding and the number biomedical publications for 132 U.S. universities. For 52 hospitals a correlation of 0.89 was found. For all 229 institutions it was found that NIH provided 91% of the boimedical research support from major federal agencies, and more than half of the total extramural biomedical research support. There was no indication of either economies or diseconomies of scale in the number of publications produced by the institutions, which ranged from a few publications per year to over 700 per year.


The ins and outs of calcium transport in squid axons: internal and external ion activation of calcium efflux. The intracellular ionized calcium concentration ([Ca2+]i) in squid axons is far below that expected at equilibrium, and Ca2+ must therefore be extruded against a large electrochemical gradient in order to maintain the steady state. In the absence of ATP, Ca efflux from internally-dialyzed axons is largely dependent on external Na, and is associated with a Cai-dependent Na influx. An Nai-dependent Ca influx and Cao-dependent Na efflux have also been observed in squid axons. The data imply that the axolemma has a "carrier" mechanism that can mediate the counterflow exchange of Na+ for Ca2+. Several observations indicate that the stoichiometry of the exchange is about 3 Na+-for-1 Ca2+:a) Ca efflux appears to be a cubic function of external Na concentration; b) Ca efflux is reduced when the membrane is depolarized; and c) the Nao-dependent Ca efflux is about 1.5 pmoles/cm2-sec when free [Ca2+]i is about 160 mum, while the Cai-dependent Na influx is about 5 pmoles/cm2sec. If the stoichiometry is 3-for-1, the Na electrochemical gradient, alone, could provide sufficient energy to maintain [Ca2+]i at about 50-200 nM. ATP also influences the Ca efflux: it appears to increase the affinity of the transport mechanism for internal Ca, but does not affect the maximum velocity of transport. Thus ATP may catalyze, but not necessarily energize Ca transport.


The influence of nucleotides on calcium fluxes. The effect of ATP and other nucleotides on calcium efflux was studied in squid axons dialyzed with Ca:ethylene glycol tetraacetic acid buffers to control the internal ionized calcium concentration. In the virtual absence of internal ATP (ca. 1 muM) a significant level of calcium efflux occurs which could be increased by the addition of internal ATP. At low concentrations of ionized calcium (ca. 200 nM), efflux increased 10-fold. At high levels of ionized calcium (ca. 100 muM), the increase was only twofold. This stimulation of efflux by ATP requires internal sodium. Conversely, ATP renders the calcium efflux insensitive to internal sodium and prevents the inhibition of calcium efflux produced by internal sodium in the absence of ATP. Of 12 nucleotides tested, only ATP, deoxy-ATP and alpha, beta-methylene ATP significantly stimulated calcium efflux. The data are interpreted as indicating that ATP induces an affinity in change in the carrier system binding calcium to the internal site, possibly by a phosphorylating step.


Steady-state calcium fluxes: membrane versus mitochondrial control of ionized calcium in axoplasm. Squid axons appear in a steady state with respect to ionized Ca when [Ca]o is ca. 3 mM and [Ca]i is ca. 30 nM. A membrane pump energized by the Na gradient across the membrane is capable of maintaining this ratio of ionized Ca if four Na enter per Ca extruded. Empirically, it is noted that if the difference between the electrochemical gradient for Na+ and that for Ca2+ is large and positive, Ca efflux is large; for a large but negative difference in the gradient, Ca influx is large. Net fluxes of Ca into the fiber are induced by Na-free solutions or stimulation. These are buffered in axoplasm principally by a high affinity Ca buffer. Mitochondria apparently do not contain large amounts of stored Ca as CN poisoning does not increase ionized Ca in axoplasm if the seawater is Ca-free.


Interactions of chlorinated hydrocarbons with steroid hormones. Effects of chlorinated hydrocarbons of the DDT class in mammals were examined. Two effects were considered: a) induction of hepatic mixed function oxidase (MFO), and b) estrogenic activities. The induction of MFO was discussed primarily with reference to the enhancement of steroid hydroxylation. In turn, the increase in steroid hydroxylation by chlorinated hydrocarbons was usually accompanied by a decrease in the biological activity of endogenous and administered steroid hormones. The estrogenic activity of chlorinated hydrocarbons was found to reside primarily in the o,p'-DDT (a major contaminant of technical grade DDT). The mechanism of the estrogenic activity by DDT homologs was explored. It appears that o,p'-DDT acts like estradiol (E2). Similarly to E2, o,p'-DDT binds to the uterine cytosolic receptor. Furthermore, like E2, o,p'-DDT is a potent inducer of certain uterine enzymes. For instance induction of ornithine decarboxylase of about 200-fold was observed with a high dose (250 mg/kg body wt); however as little as 5 mg/kg of o,p'-DDT exhibited marked induction of this enzyme--about threefold. The above activities of the chlorinated hydrocarbons were considered with respect to the potential long-term toxic effects which these compounds might elicit.


[Response of the receptive fields of the lateral geniculate body to temporal changes in the area of a light stimulus]. Neuronal responses of the cat LGB to light spots the area of which was changing in time with different speed, were studied. All the neurons responding to switching on and off of the test spot respond to changing in time of the spot area too. The on-neurons respond to enlargening of the area while the off-neurons - to its reducing. The on- and off-responses of these fields occurred at the moment of passing of the margin of reducing (growing) spot across a certain point of neuron's receptive field. This point changed when the speed of reducing (growing) of the test spot changed.


[Electrophysiologic study of trace changes in the excitability of the rat spinal cord]. In white rats, retention of the amplitude asymmetry of the monosynaptic reflex responses (MSRR) in the ventral roots of the spinal lumbosacral segments due to removal of half of the cerebellum, was studied. The MSRR asymmetry remained after the consequent spinal cord section at the thoracic level if it had existed over 20 min (fixation period) before this section. When tested with electric stimuli applied to the nerves of muscles-antagonists, the stable MSRR asymmetry could be unidirectional or reciprocal. Prolonged unilateral stimulation of the muscle nerve central end in the spinal rat with stimuli of different frequency and intensity evoked no MSRR amplitude asymmetry during subsequent bilateral testing of the same nerves. But in decerebrated rats the MSRR asymmetry has frequently appeared after such stimulation. Asymmetry of the reticular descending influence is supposed to play a major role in the trace stable changes of excitability of the spinal cord neuronal substrate as well as different capacities of different neurons (or their elements) for fixation and retention of such changes.


[Responses in the superior thoracic white rami communicantes to stimulation of the dorsolateral funiculi of the spinal cord]. In anesthetized cats, the responses in T3 white rami to stimulation of the spinal dorsolateral funiculi at C5 level displayed three typical waves. The short latency first wave is the result of stimulation of descending fibres with conduction velocity over 20 m/sec, which activate some sympathetic preganglionic neurons monosynaptically. These neurons are, probably, outside of the lateral horns and have axons with conduction velocities over 10 m/sec. The second wave is associated with the discharges of lateral horn's sympathetic preganglionic neurons disynaptically activated by descending fibres with conduction velocity about 6 m/sec.


[Effect of adrenaline on the secretory activity of the ocular ciliary body in rabbits]. In intact rabbits and in rabbits with intracerebral unilateral section of the n. oculomotorius, instillation of 2 drops of 0.1% adrenaline into the conjunctival sack increased and then decreased the intraocular pressure (IOP); i.v. administration of adrenaline (50 mcg) or electrophoresis decreased IOP. In conditions of disturbed parasympathetic innervation of the eye its sensitivity to adrenaline increased as revealed by a sharper lowering of IOP.


[Reflex responses during the early period of recovery of motor function in a transplanted limb]. In immobilized anesthetized rats, monosynaptic reflex responses before and after (3 months) the autoreplantation of the left hind limb were studied. The early period after replantation was characterized by the lowering of excitability, the increase of latency, the decrease of differences between reflex responses to nerves stimulation. Differences existed between responses to stimulation of flexors and extensors but only with a major time summation which suggested that they were due to dendrite processes in chromatotized motoneurons.


[Effect of electrical stimulation of the hypothalamus on the process of blood platelet aggregation]. Stimulation of hypothalamic ventromedial and posterior nuclei via implanted electrodes was followed by phasic changes of the blood coagulation processes and thrombocytes dynamic functions. Within the first minutes after stimulation, an increase of the blood coagulation potential, of aggregation and adhesive features of thrombocytes was observed, replaced later by reduction of thrombocytes dynamic features and by decreasing blood coagulation potential. The above changes are associated with alteration of the blood content of aggregating agents, inhibitors of aggregation, and blood coagulating factors. The hypothalamic structures are suggested to exert control over thrombocytes hemostatic functions via a humoral link.


[The anticoagulant system following intravenous administration of factor XIII and thromboplastin]. The inactivated factor XIII does not change the functional state of the anticoagulating system. The i.v. administration of thromboplastin activates the anticoagulating system in rats which cannot be prevented by an artificial rise of the titre of the inactivated factor XIII in blood. The i.v. injections of the secondary adreanlin-heparin--fibrinogen complex with higher level of the factor XIII is followed by a sharp increase in the functional activity of the anticoagulating system.


[Effect of thyroxine and 2,4-dinitrophenol on cardiac energetics]. The administrations of 1-thyrohine (20 mg/kg) for two sucessive daysin the rats or 10(-3) M 2,4-dinitrophenol (2,4-DNP) in vitro reduced the mechanical of the heart in working isolated preparations of the rat heart. Oxygen consumption of inactive heart did not react to thyroxine and significantly increased after 2,4-DNP administration. The reduction of the heart efficiency due to thyroxine is, probably, associated with a decreased efficiency of mechanochemical conjugation in the myocardium muscular fibers.


[Characteristics of atrial mechanoreceptors and elastic properties of the atria in experimental cardiac failure]. Cats developed heart failure as a result of a partial stenosis operation of the pulmonary artery. Within 10 to 25 days after the operation, pressure in the right atrium was higher than normal and the atrium diameter was larger. The dependence of atrial distension and integral mechanoreceptor activity in the right atrium on atrial pressure was studied. A possible physiological significance of the change in atrial mechanoreceptor characteristics of animals with heart failure, was investigated.


[Cationic composition of pancreatic juice and blood plasma during functional changes in the pancreas]. In chronic experiments on dogs with Pavlov's fistula, potassium and calcium concentration in the blood plasma was increased after feeding; their pancreatic concentration was lower, respectively, by 0.2 and 0.3 units/ml prior to feeding and 0.3 and 0.6 after the feeding. Sodium concentration in the pancreatic juice corresponded to its concentration in the blood plasma and did not change after feeding. Changes of sodium concentration in the blood plasma or pancreatic juice indicate disturbances in pancreatic function.


The significance of the cell surface for the homing affinity of injected lymphoid cells in mice. 51Cr-labelled lymph node cells were injected into syngeneic or non-syngeneic mice and their relative tissue distribution was compared under conditions where, for the reason of either timing or genetic combination, the host-versus-graft response could be neglected. The immigration of injected lymphoid cells to lymph nodes was markedly reduced when the recipients were non-syngeneic or when the level of glycosaminoglycans in their blood was artificially increased. In contrast, the homing affinity to the spleen was inhibited only for a relatively short period of time following stress. In the various tested situations in which the migration of cells to lymph nodes was inhibited, it seemed to be the relationship of the cell surfaces of the sessile and circulating cells which played an important role in the outcome of their interactions. This relationship may be influenced both by certain genetic differences and experimentally, for example, through adsorption.


Repair synthesis of DNA after irradiation and its modification due to radioprotection in vivo. Repair DNA synthesis was examined in bone marrow cells exposed to LD 50/30 in vivo. Intensive repair synthesis took place during the irradiation, and the increase in 3HTdR uptake prevailed over the inhibitory effect of radiation and AET upon DNA synthesis. After LD 50/30, the intensity of DNA repair was reduced. Application of AET resulted in an increase in repair DNA synthesis after irradiation, indicated by a significantly higher incorporation of 3HTdR.


Prediction of radiosensitivity of individual mice by multidimensional analysis. Ten physiological indices on each mouse were measured before an exposure to ionizing radiation. The exposure of mice to 700R of X-rays induced 45% mortality within 30 days. A prediction of death or life of each mouse was done by a multidimensional quantification. The highest success rate of prediction was obtained by using all ten indices and it resulted in 74.1%. Accordingly, it was possible to predict death of individual mice exposed to a dose around LD50 (30) with a high rate of success. When one selected five indices out of the ten indices by some criterion, the success rate of prediction decreased to 67.1%.


The role of bursa of Fabricius and thymus in antibody-mediated allograft rejection in ducks. Duck immune sera that are capable of destroying the tolerated skin allografts require the presence of functional host's lymphoid cells for a successful course of the rejection reaction. The effective sera are not able to destroy the grafts in birds surgically bursectomized or thymectomized at hatching. This deficiency can be repaired by thymic, not bursal, implants in bursectomized or thymectomized graft hosts. Similarly, measurements of the radioactivity after application of 125I-labelled gamma globulin to allografted or autografted ducklings confirm a major role of the bursa of Fabricius and thymus in the destruction of the tolerated skin allografts by immune serum.


Effect of inflammation on serum glycoproteins in rabbits. Quantitative changes in the concentration of rabbit serum proteins and glycoproteins accompanying a non-specific injury (terpentine oil inflammation) were studied by conventional electrophoretic and quantitative crossed immunoelectrophoretic analysis. Most significant changes were observed in the alpha2- and beta-globulin region as well as in some individual glycoproteins (haptoglobin, ceruloplasmin, IgM globulin). In the paper the parallel changes in sugar components of glycoproteins were also recorded.


The effect of thymosin application upon radiation sickness in mice. The mechanism of thymosin effect upon radiation sickness was analyzed in mice. Thymosin (fraction 5) applied before and after a whole-body radiation exposure increased the LD 50/30 of treated animals by 250R. In mice exposed to 500R, thymosin treatment resulted in a faster recovery of haemopoiesis and lymphopoiesis, as indicated by higher bone marrow cellularity, higher lymph node, thymus and spleen weights, and greater 59Fe uptake in the spleen and femur and 125IUdR uptake in the spleens, femur and thymus. The results provide an indication that thymus and its humoral factor markedly influence the haemopoietic stem cells in the population surviving the sublethal irradiation of an organism. They further suggest the existence of feed-back mechanisms between the thymus and harmopoiesis.


Proliferation kinetics and lethality after irradiation; modification by radioprotection. By means of radioprotection, it was shown that a correlation exists after LD 50/30 between radiation-induced changes in cellular proliferation of critical radiosensitive tissue (bone marrow) and lethality, both in the time course and in the degree of the effect. Close correspondence between proliferation changes after irradiation and radiation lethality indicates that the inhibition of proliferation activity may play a major role in the mechanism of the death of irradiated organisms. A modification of cellular proliferation results in a change in radiation mortality. Pretreatment with the radioprotective compound AET leads to a moderation of both the inhibitory effect of radiation upon proliferation and radiation lethality.


Changing patterns of migration between metropolitan and nonmetropolitan areas in the United States: recent evidence. Data from the 1975 Current Population Survey confirm that, during 1970-1975, there was a reversal of the traditional net migration stream between metropolitan and nonmetropolitan areas in the United States. During this period, there was net in-migration of 1,600,000 persons to nonmetropolitan areas, in contrast to net out-migration of 350,000 persons from these areas in 1965-1970. Reversal was caused by a 12 percent decrease in the number of nonmetropolitan out-migrants and a 23 percent increase in the number of SMSA residents moving to nonmetropolitan territory over 1965-1970 levels. While some changes in the size of migration streams were due to changes in age structures and population bases in metropolitan and nonmetropolitan areas, they were caused primarily by real shifts in out-migration propensities at practically all ages in both areas.


Recent urbanization trends in Peninsular Malaysia. The pace of urbanization in Peninsular Malaysia was slower in the most recent intercensal interval, 1957 to 1970, than in the previous period, 1947 to 1957. Most of the small change in the rural-urban balance from 1957 to 1970 appears due to the growth of towns into the urban classification rather than to a redistribution of population into the previous urban settlements. A number of towns in Peninsular Malaysia do show exceptional growth from 1957 to 1970, but there seems to be no clear relationship between a city's size and its subsequent growth. The rural areas on the outskirts of the largest cities do show rapid growth, especially the periphery of the capital city. It appears that neither the classic model of urbanization based upon Western experience nor the over-urbanization thesis explain the urbanization process in Peninsular Malaysia.


The effect of subsidized family planning services on reproductive behavior in the United States, 1969-1974. This paper evaluates the impact of federally subsidized family planning programs in the United States, from 1969 to 1974, on the reproductive behavior of ever-married women, 15-44 years old. The study began with an experimental design and the random assigment of areas to treatment and control but was completed as a multivariate analysis, treating program input as an interval-scaled independent variable. Using "before" and "after" area sample surveys and patient service data from operating programs, the demographic impact of the program was estimated. The impact detected was nonsignificant; according to our analysis, overall use of physician-administered contraception was not affected by the subsidized programs. The only program-induced change of activity related to reproduction that we recorded was increased use of subsidized services in study areas with high program input and increased use of private physician services where program input was low. These findings need to be interpreted with the caution usually exercised in evaluating imperfect field experiments.


Motivations for the use of birth control: evidence from West Africa. A conventional assumption in the family planning literature is that birth control in developing countries is first adopted by high parity women who wish to cease childbearing. The empirical support for this belief has mainly been drawn from interview surveys on the motivations for, and the timing of, the inception of birth control among married women in areas where there is no cultural precedent for birth spacing by traditional means. This study, on the other hand, is based on data drawn from an area sample of 6,606 women, married or single, aged 15-59, in Ibadan, Nigeria, where there is a tradition for the practice of abstinence after a birth for the purpose of birth spacing. The Nigerian pattern revealed in the data presented here is indeed distinctive in many respects: (a) although premarital sex is prevalent, levels of premarital contraception are high; and (b) within marriage, spacing is the most prominent motivation for contraceptive practice, more important than the limitation of family size.


Abortion and family-binding models: fertility limitation in Hungary. This paper demonstrates how family-building models can be used for checking the quality of abortion data. A family-building model, called FERMODA, is presented and used to check whether the available data on abortion for Hungary are consistent with Hungarian data on other aspects of family building. Model cohorts are generated, using in FERMODA the proportions of women married and the birth and abortion rates of two selected Hungarian cohorts. The estimates obtained from the simulated cohorts concerning use of contraception are compared with the information available on contraception, and, on the basis of this comparison, a judgment is made about the quality of abortion data for Hungary.


Some extensions of the Keyfitz momentum relationship. A stable population, such that the total birthrate B(t) = Boerot, is abruptly altered by modifying the age-specific birth rate, m(x). The survivor function remains unaltered. The modified population ultimately settles down to a stable behavior, such that B(t) = B1er1t. It is shown that B1/Bo = (Ro-R1)/¿e1(ro-r1)RoZ1], where Ro, R1 are the net reproduction rates before and after the change, and Za = expected age giving birth for the stable population after the change. The age structure and transients resulting from the change are also described. The effect of an abrupt change in the survivor function l(x) is also investigated for the simple case where the change is caused by altering l(x) to e-lambdaxl(x). It is shown that the above ratio becomes B1/Bo = N1/No = [1 - zota o e-kxg(x)dx]/Z1lambda, where N refers to the numbers in the population, k = ro + lambda, and g(x) = m(x)l(x), the value before the change. A measure for the reproductive worth of the population is also established.


Influence of instantaneous fertility decline to replacement level on population growth: an alternative model. If age-specific birth rate mx of a stable population drop abruptly to mx/Ro, where Ro is the net reproduction rate, then, according to Keyfitz, the size of the ultimate stationary population relative to that at the beginning of the process is given by I = beoo(Ro - 1)/(rmuRo), where b and r are the birth rate and the rate of growth, respectively, of the stable population, eoo the life expectancy at birth, and mu the average age at childbirth in resulting stationary population. Noting that the decline in mx need not necessarily be uniform, investigation has veen carried out to examine the effect on I when fertility decline is more rapid at higher ages. In particular, the effect of the reduced age-specific rates such as mxe-rx (which also produces a stationary population) has been analyzed, and simplifications of the results carried out separately for three different models of the net maternity function. It has also been shown the when mx drops abruptly to some m* x, where the form of m*x need not be specified except for the restriction that the resulting population will be stationary, the value of the index can be approximately obtained from I* = beoo (1 - rmu/2), where mu is the average age at childbearing of theinitial stable population.


Sensitivity analysis of discrete-time interregional population systems. This paper shows analytically how (a) the long-run growth rate and (b) the long-run proportional distribution of an interregional population system with a time-homogeneous structural matrix are affected by small changes or errors in (a) the natural growth rates of individual regions and (b) the interregional migration rates. Furthermore, the analytic results are applied to an eight-region Canadian population system. Finally, it is claimed that the method introduced here can be easily applied to sensitivity analysis of both the intrinsic growth rate and the "stable" age-composition of the Leslie model with respect to changes in age-specific birth and survival rates.


Life table techniques for multiple-cause mortality. A lethal defect-wear model of mortality is presented which rationalizes the assumption of independent risks when death may be due to more than a single condition. Under this model, it is shown how competing risk theory and standard categorical data methods may be merged in a unified approach to the analysis of multiple-cause mortality data. The methodology is used to analyze linkages among diseases in the mortality data and evaluate the implication of the elimination of patterns of morbid states for multiple-cause mortality data from deaths occurring in 1969 in North Carolina.


A note on migration and employment.

A note on migration and employment. This paper examines the nature of the relation between migration and employment. A preliminary investigation confirms a previous observation that the employment rate of migrants is generally lower than that of nonmigrants. A further analysis, however, suggests that this does not mean that migration has no effect on employment; in fact, the two appear to be strongly related. Migration enables some unemployed and initially disadvantaged persons to improve their employment status, making it more nearly comparable, though not equal, to that of the general population.


Race and intra-urban migration.

Race and intra-urban migration. Data from the urban renewal experience in Syracuse, New York are used to examine the impact of race on patterns of intra-urban migration. The results show that, overall, the migration patterns exhibited an exponential decay in frequency with increasing distance. Both blacks and whites display this pattern, but blacks tend to cluster more closely around the point of origin. Indirect evidence is developed to show that this phenomenon is due to blacks and whites having different access to information about housing, which ultimately maintains housing segregation.


An instance of reverse heaping of ages.

An instance of reverse heaping of ages. This note reports on an interesting example of reverse heaping of ages for data from the Saudi Arabian social insurance system. Peaks occur for the number of workers at ages corresponding to years of birth ending in zeros and fives, while there are troughs at such  ages for the average monthly wages. Such troughs almost certainly are the result of workers with less education using a rounded year of birth, and, correspondingly, such workers would tend to have lower earnings.


[Sebaceous hyperplasias, kerato-acanthomas, epitheliomas of the face and cancer of the colon. A new entity?]. Numerous skin lesions: sebaceous hyperplasias, benign acanthoma, keratoacanthomas and squamous cell epitheliomas appeared on the face, especially on the nose, on the cheeks and around the lips of a 45-year-old obese man with mild diabetes. In 1969, an adenocarcinoma had been found in the rectosigmoid and another one in the colon. In 1974, an excision of a well-differenciated epidermoid carcinoma was performed in the right external auditory meatus. A rectoscopy showed a micropolyp at the rectosigmoid junction. In 1975, an abdominal exploration was performed following a sudden relapse of about 50 skin lesions in the face, partly sebaceous adenomas, partly sebaceous gland epitheliomas, and about 10 precancerous lesions on the dorsum of the hands. A villous adenoma of the colon was removed. Inheritance appears to the autosomal dominant with variability in the expressiveness of the cutaneo-intestinal symptoms.


Pyoderma gangrenosum in immunosuppressed patients. Two cases with pyoderma gangrenosum are presented. The course, in both cases, suggested that immunosuppressive therapy may play an etiological role in the disease. The first was a kidney recipient receiving prednisone and azathioprine and the second, a patient with pemphigus vulgaris who was treated with prednisone and methotrexate.


Primary eruption of prurigo simplex subacuta. 28 patients with typical picture of prurigo simplex subacuta were examined for the primary eruption. In all patients, the first visible lesion was a papule, at the top of which a vesicular element was never seen. 46 biopsy specimens of the initial eruption were serially sectioned. The histological changes were found in connection with hair follicles, which consisted of spongiosis and mononuclear cell migration at the follicular epidermis and perifollicular infiltrates of mononuclear cells.


[Urinary excretion of catecholamines in obese subjects and in diabetics (author's transl)]. 95 obese subjects, 40 diabetics and 22 normal controls were investigated. The weight of all obese subjects was at least 20% higher than the ideal weight. Catecholamine excretion was determined a few days after hospitalization to minimize the influence of environmental changes. Spectrofluorimetric estimation of adrenaline and noradrenaline in the urine was carried out according to the method of von Euler and Lihajko. Statistical analysis of the results showed a significant increase in both adrenaline and noradrenaline excretion in the group of obeses subjects compared with the diabetics. The increased catecholamine excretion may represent the response of the adrenal medulla to the stress of the disease. Such an increase may be responsible for perpheral insulin resistence and hence acts as a diabetogenic factor. The results obtained emphasize the influence of catecholamines on insulin responsiveness, possibly constituting a major contribution to the diabetic state.


[Changes in carbohydrate metabolism and efficiency of hypoglycemic drugs related to the light dark cycle in rats. A study on stimulated diaphragm (author's transl)]. A study of glucose uptake and lactate release was performed on isolated diaphragm stimulated regularly by an electric device. This stimulated model is much more sensitive than the motionless diaphragm preparation in the Warburg apparatus. The diaphragms take up twice as much glucose and release one and a half times more lactate during summer than during winter. This increase relates to lighting conditions. It is suppressed even during summer, if rats are maintained in darkness for 15 days before the experiment, other factors remaining unchanged. Several antidiabetic drugs (insulin, metformin, phenformin, buformin), active on the stimulated diaphragm, have their effects reduced or suppressed when animals are exposed to intense light; they regain their effect even during summer, if the animals are kept in the dark. The mechanism and practical implication of these findings are discussed.


[Studies of lipoprotein lipase activity and adipocyte characteristics in the human: effect of obesity and diabetes (author's transl)]. Adipose tissue lipoprotein lipase activity (LPLA) and cellularity have been studied in controls, in diabetic or non-diabetic obese subjects and in insulin dependent diabetic patients. LPLA is increased in diabetic or non-diabetic obese subjects and in insulin dependent diabetic patients. LPLA is increased in diabetic or non-diabetic obese subjects (p less than 0.02) and decreased in insulin dependent diabetic patients (p less than 0.02). Adipocyte size is larger in obese subjects, whether diabetic or not (p less than 0.05). As defined by LPLA and cell size means, the different groups are related linearly. The implications of this relationship between LPLA and adipocyte size are considered.


Growth hormone stimulating the growth of arterial medial cells in vitro. Absence of effect of insulin. Earlier studies have shown a stimulatory effect of diabetic serum on the growth of rabbit aortic medial cell cultures. Growth media supplemented with normal serum with added insulin (50-2,000 muU./ml. serum) did not enhance the growth of the medial cell cultures. Control media containing serum from recent diabetics with low insulin concentration stimulated the growth (2p less than 0.01). Supplementation of normal serum with human growth hormone (final concentration 1-5 ng./ml. medium) resulted in a significant enhancement of growth (2p less than 0.005). The growth-promoting effect of growth hormone was not detectable with lower concentrations (0.5 ng. and 0.1 ng./ml. medium). The growth effect of the low concentration of growth hormone could not be augmented by increasing the concentration of glucose in the incubation medium. Growth hormone in an amount of 1 ng./ml. medium increased both the number of 3H-thymidine-labeled cells as identified by autoradiography and the number of mitotic bodies (2p less than 0.005 and 2 p less than 0.025). The present results demonstrate that the growth-stimulating factor(s) in diabetic human serum described earlier is not insulin but may well be growth hormone.


Effect of environmental temperature on glucose-induced insulin response in the newborn rat. Blood glucose and plasma insulin and glucagon concentrations were determined in full-term rats delivered by cesarean section and exposed to 37 degrees C. or 24 degrees C. environmental temperature during the first hours of extrauterine life. When newborn rats were maintained at thermal neutrality (37 degrees C.), a transient period of hypoglycemia of two hours occurred, associated with a rapid fall in plasma insulin and a rise in plasma glucagon concentrations. During cold exposure (24 degrees C.), the blood glucose level remained stable over the four hours studied; the decrease of plasma insulin was sluggish while the rise of plasma glucagon was unchanged. In newborn rats maintained at 37 degrees C., an intraperitoneal glucose load one hour after delivery produced a marked rise in blood glucose and plasma insulin concentrations one hour later. The distribution of experimental points suggested a sigmoidal dose-response curve. By contrast in newborn rats kept at room temperature (24 degrees C.) the same glucose load did not induce any increase in plasma insulin in spite of hyperglycemia. However, phentolamine resulted in pronounced plasma insulin rise in hypothermic newborns in response to glucose administration. From these observations it is concluded that the in-vivo unresponsiveness of the beta cells to glucose at birth, reported by others, is mainly due to the experimental conditions.


Reversal of somatostatin inhibition of insulin and glucagon secretion. These studies were designed to elucidate the mechanism of inhibitory action of somatostatin (SRIF) on glucagon (IRG) and insulin (IRI) secretion. Studies were carried out in the unrecirculated isolated rat pancreas perfusion with arginine 19.2 mM and glucose 5.5 mM as stimulus primarily for IRG but also IRI secretion. The effects of excess Ca++ (15.2 mEq./L.) and excess K+ (12.8 mEq./L.) on IRG, IRI, and the SRIF-inhibited pancreas were studied. Ca++ excess in five perfusions strikingly stimulated IRG secretion (+92 per cent) but only stabilized IRI secretion compared with control perfusions. K+ excess (in seven perfusions) markedly inhibited IRG secretion (-39 per cent) while stimulating IRI secretion (+16 per cent). Restoration of normal concentrations of K+ resulted in a rebound of IRG to levels 120 per cent that of controls. SRIF, at concentrations from 0.1-20 ng./ml., produced inhibition of both IRG and IRI. In 11 perfusions, with SRIF at 10 ng./ml., IRG decreased more than IRI (-75.2 per cent IRG and -46.9 per cent IRI). In five perfusions, addition of Ca++ (15.2 mEq./L.) 10 minutes after SRIF was started resulted in a reversal of IRG inhibition to 69.4 per cent and IRI to 73.2 per cent of the arginine controls. The reversal by Ca++ of SRIF effect on IRG was greater at higher concentrations of Ca++, suggesting some form of competition. In four perfusions, excess K+ reversed SRIF-induced IRI inhibition to 79.6 per cent that of controls but had no effect on IRG inhibition. Studies in vitro with isolated islets revealed that SRIF (2 mug./ml.) inhibited 45Ca uptake of islets as did epinephrine (10(-5) M). It was concluded that SRIF-induced inhibition of hormone release appears related to an action on Ca++ uptake.


Treatment of insulin-induced lipoatrophy. Twenty children with insulin-induced lipoatrophy were successfully treated by injecting the insulin into the lipoatrophic area. In 10 children insulin therapy was replaced by monocomponent insulins, while the other 10 children were treated with the insulins they previously used. It is concluded that both monocomponent and less purified insulins are suitable for treating the complication of insulin therapy when the insulin is injected into the lipoatrophic area.


Abnormal carbohydrate metabolism in amyotrophic lateral sclerosis and Parkinsonism-dementia on Guam. Amyotrophic lateral sclerosis and Parkinsonism-dementia are unusually prevalent on Guam. Carbohydrate metabolism was studied in 110 patients with evidence diagnostic of or suspecious for these diseases. The combined incidence of known diabetes in 29 per cent of them plus a high percentage of glucose tolerance tests interpreted as abnormal, even when most age-related criteria were considered, was considerably higher than the incidence of abnormal carbohydrate metabolism reported elsewhere in the general population of the United States, the tropical Pacific area, or in recent surveys on Guam itself. The diabetes was generally mild in nature and noteworthy for a lack of retinopathy and other complications. Hypertension, hypercholesterolemia, and hyperuricemia, although highly prevalent, were not consistently associated with abnormal glucose metabolism. Similarly, no consistent association was demonstrated with such factors as age, muscle atrophy, or physical activity.


Insulin, glucagon, and somatostatin in normal physiology and diabetes mellitus. Studies are reviewed in which the roles of insulin and glucagon in normal physiology and in diabetes are examined. In normal man, glucose ingestion is accompanied by a rise in insulin and fall in glucagon and is primarily disposed of in the liver, an organ sensitive to both hormones. However, infusions of glucagon in physiologic amounts indicate that insulin secretion rather than glucagon inhibition is the primary factor determining glucose disposal. Furthermore, minor elevations in blood glucose elicit increments in insulin concentration and inhibition of hepatic glucose output in the absence of changes in plasma glucagon. The primary physiologic role of glucagon is to prevent the hypoglycemia that would otherwise accompany noncarbohydrate (protein)-mediated insulin secretion. In diabetic as well as normal patients the stimulatory effect of glucagon on hepatic glucose production is evanescent. Increases in glucagon or changes in the I/G ratio can bring about deterioration in glucose tolerance or in diabetic control only so long as absolute insulin deficiency is present or pharmacologic elevations in glucagon are produced. After somatostatin administration, prolonged hypoinsulinemia in normal subjects is observed to result in fasting hyperglycemia in the absence of basal glucagon secretion. In diabetic patients the improvement in postprandial hyperglycemia produced by somatostatin can be accounted for by its inhibitory action on carbohydrate absorption in the gastrointestinal tract. It is concluded that insulin deficiency is the primary pathophysiologic disturbance in diabetes. While glocagon may worsen the consequences of insulin lack, it is neither sufficient nor necessary for the development of diabetes.


Early detection of diabetic visceral neuropathy. An electrophysiologic study of bladder and urethral innervation. The segmental and supraspinal innervation of the detrusor muscle and periurethral striated musculature was studied in 27 patients with diabetes mellitus by gas cystometry, integrated sphincter electromyography, and spinal evoked-response latency measurements. Slowing of neural conduction velocities was a consistent finding in all the patients, even when cystometry did not show abnormalities. Thus, neuropathy in the segmental innervation of the bladder and urethra was documented.


Leucocyte-migration inhibition induced by uveoretinal antigen in patients with diabetic retinopathy. Leucocyte-migration inhibition was to determine the state of hypersensitivity in 65 diabetic patients with different stages of retinopathy and 21 nondiabetic controls. About one third of the patients with simple or proliferative retinopathy exhibited significant leucocyte-migration inhibition of 0.2 mg/ml. protein concentration of uvreoretinal antigen. In contrast, only one of 15 patients with minimal retinopathy and none of the controls showed significant leucocyte-migration inhibition. Corneal and lenticular antigens did not evoke a cellular immune response in any of the tested individuals. These findings suggest that cell-mediated hypersensitivity to uveoretinal antigen may develop in diabetic patients with prolonged, progressive, simple or proliferative retinopathy.


Community screening for diabetes by blood glucose measurement. Results of a five-year experience. The Diabetes Association of greater Cleveland screened 307,000 individuals in the metropolitan area for diabetes with a 75-gm. oral load of carbohydrate. Of these subjects 12,600 (4.1 per cent) had a two-capillary blood glucose level of greater than 139 mg. per cent and were defined as positive. Seventy per cent of the positives were retested, and 65 per cent of these again had two-hour levels greater than 139 mg. per cent. Seventy-one per cent of the original screening values were between 104 and 199 mg. per cent. The rate of positivity on retesting increased with the original screening bracket reaching 90 per cent at an original screening level of 240 mg. per cent or higher. The frequency of positive retests also increased with age irrespective of whether the original screening level was less than or greater than 200 mg. per cent. The implications of this large detection experience for conducting future mass surveys for diabetes are discussed.


Effects of pregnancy on hemoglobin AIc in normal, gestational diabetic, and diabetic women. Hemoglobin AIc, a normal minor hemoglobin, has glucose linked by a Schiff base to the N-terminal end of the beta chain. The glucose interferes with the binding of 2,3 diphosphoglycerate, probably resulting in an increased affinity of that hemoglobin for oxygen. Hb AIc is increased to twice normal levels in juvenile-onset (insulin-dependent) diabetes. In the present studies, the Hb AIc, when expressed as per cent of total hemoglobin, was found to be elevated slightly in pregnany normal (m = 6.97 per cent), pregnant nondiabetic obese (m = 6.89 per cent), and gestationally diabetic subjects (m = 8.77 per cent) above that of normal females (m = 5.68 per cent). A remarkable difference was observed between the nonpregnant diabetics (m = 12.77 per cent) and the pregnant diabetics (m = 8.46 per cent). This decrease in the level of Hb AIc in diabetics who are pregnant more than 30 weeks may reflect either a better state of diabetic control and/or a compensatory mechanism to protect the fetus by facilitating oxygen exchange from mother to fetus.


Scanning electron microscopy of cell-surface changes in methylnitrosurea (MNU)-treated rat bladders in vivo and in vitro. Scanning electron microscopy has been used (1) to characterize epithelial cells of bladders from normal rats and from rats treated with a single initiating but non-carcinogenic dose of 2 mg methylnitrosurea (MNU), 24 h and 6 weeks after treatment; and (2) to compare morphological aspects of epithelial differentiation in organ culture of bladder explants taken from untreated and MNU-treated rats at these time intervals. There are marked differences in vivo between the surface organization of normal urothelium and urothelium undergoing reversible hyperplasia following MNU treatment. Maturation of the normal rat bladder epithelium in vivo is shown to be related to a series of well-defined cell-surface changes readily identified by SEM. By contrast the maturation response is perturbed in the hyperplastic epithelium; the cells lose their ability to differentiate normally and form instead an excess of stubby globular microvilli which project from the cell surface. In organ culture, maturation of normal bladder epithelium (both in re-epithelialized areas of the explant and in areas of epithelial outgrowth over cellulose acetate substrates) can be also related to a series of cell surface changes showing close similarities to those in vivo. However, epithelial maturation remains defective in organ cultures of bladders from MNU-treated animals. The closely parallel behaviour of the bladder epithelium in vivo and in vitro in both normal and treated tissues underlines the potential value of the bladder organ culture system for studying the comparative biology of hyperplastic development produced by a single initiating dose of MNU and suggests it will be useful with which to study carcinogenesis following multiple doses of MNU.


Effect of rate of replication upon transcription in chick embryo limb bud mesenchyme cells in organ culture. In partially synchronized organ cultures of limb bud mesenchyme cells of the 3 1/2-day chick embryo the net accumulation of RNA per cell, including DNA-like RNA, is greater than in randomly dividing cells. Based on levels of newly synthesized DNA, RNA accumulation is greater in the last half of the S period when the rate of DNA synthesis is slower. The ratio of newly synthesized RNA, including DNA-like RNA, to newly.synthesized DNA, is also increased when the rate of DNA replication is reduced with cytosine arabinoside and hydroxyurea. The proportion of newly synthesized non-histone protein to total protein in the chromatin increased with a slower rate of DNA replication and this may account for the augmented transcription. At equivalent levels of inhibition of protein synthesis with the arginine analogue, canavanine, and cycloheximide, it was found that canavanine was more effective in reducing the rate of DNA replication. This suggests that histone synthesis plays a role in controlling the rate of DNA replication. The importance of such findings is that a difference in rate of replication of the same DNA sequences in two cells could cause differential transcription resulting in these cells expressing diverse patterns of cell differentiation.


Hormone-induced alterations in nonhistone protein. Methylation and phosphorylation in Sciara coprophila. Methylation and phosphorylation of chromosomal nonhistone protein (NHP) has been demonstrated in the salivary gland cells of diptera [5, 7] and implicated in the control of gene expression [35, 36]. Furthermore, hormones can stimulate methyl and phosphoryl side chain metabolism and thus enhance template activity. Salivary glands from late fourth instar female larvae of Sciara coprophila (cortisone-supplemented and normal diet) were incubated in 3H-uridine (10 muCi/ml), 3H-thymidine (10 muCi/ml), 3H-methyl-methionine (20 muCi/ml), 35S-methionine (10 muCi/ml) and 32P-orthophosphate (1 mc/ml), for varying time periods, to measure RNA synthesis, DNA synthesis, methylation, protein synthesis and phosphorylation, respectively. Following selective extraction of lipid, histone and nucleic acids, glands were prepared for light microscope autoradiography. A more specific labelling pattern, as well as increased grain number on particular bands, interbands and bulbs, was noted on chromosomes from cortisone-fed larvae incubated in 3H-methyl-methionine for 1 min when compared with larvae on the standard diet. Cortisone also increased RNA synthesis and nucleoprotein phosphorylation, but not DNA or protein synthesis. In summary, cortisone enhances the specificity and degree of NHP methylation and phosphorylation at discrete chromosomal loci, i.e. alterations in side chain metabolism which may be responsible for increased RNA synthesis.


Ontogeny of LDH-isozymes in Mexican Axolotl, Ambystoma mexicanum by thin-layer isoelectric focusing. The ontogeny of lactate dehydrogenase (LDH) isozymes in developing Mexican axolotl, Ambystoma mexicanum was investigated by thin-layer isoelectric focusing in polyacrylamide gel. The isoelectric points (pI values) of the isozymes were determined. The minor components generally remained masked during conventional electrophoresis, but became sharp as isofocusing progressed. We identified in developing eggs and embryos five major LDH isozymes, which could also be traced in the ovarian eggs. All these isozymes, except LDH-1, consisted of one major and one minor component. Heterogeneity in axolotl LDH is reported for the first time. The separated isozymes had pI values from 5.24-6.60. Contrary to observations made by others, it was found that the anodal forms of LDH (PIs 5.24-5.80) were prominent throughout, while the remainder (pIs 6.16-6.60) gradually lost their stainability. It thus appears that isoelectric focusing is a possible method for the analysis of protein mixtures and can be successfully applied to problems of differentiation.


Deconjugation of bile acids by human intestinal bacteria. The purpose of this report is to present the deconjugation of bile acids by numbers of strains of bacteria in the small intestine and feces. The small intestinal juice was aseptically aspirated by a double lumen tube with a rubber cover on the tip devised by us ("Fukushima Type 1"). Bile acids were analyzed with thin layer chromatography. 1) Among aerobic bacteria, species of which all of the strains split conjugated bile acids was enterococcus, and most of the strains split were Staphylococcus (S.) epidermidis and Lactobacillus (L.) bifidus. Species of which none of the strains split were Escherichia (E.) coli, E. communior, E. freundii, L. plantarum, L. acidophilus, L. buchneri, L. cellobiosus, L. bulgaricus, S. aureus, Aerobacter aerogenes, Pseudomonas aeruginosa, candida, proteus, serratia, and almost none of the species split was Intermediate coliform bacilli. 2) Among anaerobic bacteria, species of which all of the strains split were Bacteroides (B.) vulgatus, B. thetaiotaomicron, B. uniformis, Corynebacterium (C.) granulosum, C. avidum, Peptostreptococcus (Peptostrept.) putridus, Eubacterium (Eubact.) lentum, Peptococcus (Pept.) grigoroffii, Pept. anaerobius, Veillonella (V.) orbiculus, and most of the strains split were Coryne. diphtheroides, Eubact. parvum, Peptostrept. intermedius. Species of which none of the strains split were Coryne, parvum, Peptostrept. micros, V. alcalescens, V. parvula, Catenabacterium (Catena.) catenaforme, and Catena. filamentosum. 3) All or none, or almost all or none, of the strains of each species tested split conjugated bile acids, and it seems probably that the presence or absence of this ability would be a proper character of eachspecies.


Mucous barrier and peptic ulcer of the stomach. Mucous barrier was searched by the histochemical method of mucopolysaccharides and by the measurement of precipitated mucus of gastric juice. The neutral polysaccharide stored within the surface epithelial cells must be a source of the mucus of the gastric juice. The storage of the polysaccaride was decreased by a long-term stimulation by histamine, and the precipitated mucus volume was also decreased shortly after the stimulation. Therefore, some kind of the stimulation for the gastric secretion must be avoided for prevention of peptic ulcer. The oral administration of the sulfuric polysaccharide extracted from seaweed prevented the occurrence of experimental ulcer. It may be concluded that the exogeneous polysaccaride can take the place of the endogenous polysaccharide.


Effects of anticancer agents of the intestinal epithelium. A morphologic study. In order to make clear the pathophysiology of digestive symptoms which are caused with anticancer agents, three anticancer agents, i.e., mitomycin C, 5-FU and cytosine arabinoside were administered pre-operatively, and the ultrastructure of the intestinal epithelium, especially that of absorptive cells, were studied on the specimens collected intra-operatively. In view of the finding that severe degeneration occurred inside cytoplasms, chiefly their nuclei, it was surmised that the biosynthesis and supply of proteins such as digestive enzymes were not amply carried on; hence, the chemotherapy could give rise to severe digestion and absorption disorders. It appeared necessary to further study the dosage and dosage schedule of the anticancer agents, along with the necessity for taking ample care of patients presenting such disorders.


Consideration of hepatic factor influence on drip infusion cholangiography. The plasma disappearance rate (K) and transfer rate constants for the two compartmental system of Indocyanine Green (ICG) were calculated in visualized and nonvisualized cases of the biliary tract with hepatobiliary disease using drip infusion cholangiography (DIC). In nonvisualized cases with hepatocellular disorder K and the fractional hepatic removal rate mainly decreased, and in nonvisualized cases with cholelithiasis the fractional biliary secretory rate significantly decreased by DIC-A, utilizing it as a screening test. Three methods (B,C and D) of drip infusion cholangiography were established according to the result of the I-CG test. Through DIC-B, C- or -D in addition to DIC-A the visualization of the biliary tract significantly elevated in patients with hepatocellular disorder and cholelithiasis. These results were confirmed using 131I-iodipamide. In some cases the serum transaminase activity elevated, but the elevation was temporary.


Serum amylase isozyme changes in chronic pancreatitis and their clinical significance. The diagnostic usefulness of serum amylase isozyme measurement was investigated in 17 cases of definite chronic pancreatitis and 13 cases of suspected chronic pancreatitis, a total of 30 cases. Six types of serum isoamylase patterns were distinguished according to the character of the two main amylase activities at the fraction of fast-gamma globulin and pre-gamma globulin. The amylase activity of the fast-gamma fraction rises in acute exacerbation, and falls in cases of chronic calcifying pancreatitis and in cases with a marked decrease in pancreatic exocrine function. Especially, a fall in fast-gamma amylase activity excellently reflects a decrease in pancreatic enzyme production. The measurement of amylase activity at the fast-gamma fraction therefore appears to be a useful method for assessing pancreatic damage. The significance of a frequent rise in pre-gamma amylase activity in chronic pancreatitis remains unknown.


New insertion technique in colonoscopy, forming N-loop and using a stiffening cord. New insertion technique in colonoscopy with a middle length colonscope which is easy to be handled and without guidance of fluoroscopy was reported. Forming a small N-loop at the sigmoid colon, it was easy to pass the sigmoid colon where is one of the most difficult points to pass through. Further, using a differing cord, the sigmoid colon and the transverse colon were easily straightened and no more loop was seen. With this technique, ileocecal area was observed in 26 of 30 cases (86.7%) and its average time for the insertion required only 17.4 minutes. Therefore, with this technique ,it is emphasized that we can easily observed almost all parts of the colonic mucosa and also terminal ileum without the fluoroscopic control.


Thymus abnormalities in ulcerative colitis- comparative study with other autoimmune diseases. Since the thymus is thought to play an important role in the pathogenesis of ulcerative colitis, thymus abnormalities were studied on 18 cases of ulcerative colitis by using pneumomediastinography and histopathological examination. We have compared the thymic abnormality of ulcerative colitis with that of 104 cases of variety of autoimmune diseases. The denser and larger thymic shadow was seen in ulcerative colitis and this finding was same as in other autoimmune diseases. But the thymic size in ulcerative colitis was the largest in all examined autoimmune diseases. The incidence of thymic lymphoid follicle formation in ulcerative colitis was significantly higher than that of accidental death and this high incidence of lymphoid follicle formation is similar to other autoimmune diseases. We suggested that ulcerative colitis might be caused by the abnormal thymus dependent system.


An autopsy case of Cronkhite-Canada syndrome. An autopsy case of Cronkhite-Canada's syndrome characterized by diffuse gastrointestinal polyposis, alopetia, onychodystrophia and pigmentation of the skin is reported. The patient, 51 year-old-male, died with general weakness and pneumonia at 6 months after the first notice of alopetia anorexia and weight loss. Numerous and various sized polyps and polypoid lesions were revealed in the gastrointestinal tracts at the autopsy. The microscopic pictures of the lesions were composed of hyperplastic or papillary adenomatous polyps with hyperplasia of mucosa epithelium. In some of the lesions, the glands are cystically dilated containing mucous. Lymph vessels of thelamina propria and the submucosa benerked chronic inflammatory infiltrate was noted. The present report is described the histopathological findings of the gastrointestinal lesions with Cronkhite-Canada syndrome and discussed with literature.


Studies on the relationship between the histological changes and liver cell function or plasma proteins in hepatic diseases. Histological changes of liver biopsy specimens were compared with functioning liver cell mass estimated by an index, ICG capacity, and with plasma levels of various proteins, in 85 patients with liver diseases. IGC capacity was inversely proportional to the degrees of liver cell degeneration and lymphocyte infiltration in the portal tracts and parenchyma, in contrast to plasma disappearance rate of ICG (K), which was inversely proportional to the degrees of portal tract fibrosis and bridge formation. Among the plasma proteins synthesized in the liver, the plasma levels of prealbumin, and alpha1-acid glycoprotein showed the tendencies to decrease with the increase in the degrees of liver cell degeneration. The levels of ceruloplasmin, haptoglobin beta1A/C and transferrin were proportional to the degree of the degeneration. Plasma albumin had no correlation to any histological change. The plasma levels of gamma-globulin and IgG were both proportional to the degrees of portal tract fibrosis and bridge formation. IgM also paralleled to the degree of the fibrosis. The level of IgA was inversely proportional to the degree of liver cell swelling. It was concluded that quantitative estimations of some histological changes in the liver are valuable for the estimations of liver function and the grade of the diseases of the liver.


Investigation of the hepatic excretion mechanism of indocyanine green in patients with liver disease. The purpose of the present paper is to clarify the disturbance of the indocyanine green (ICG) uptake-excretion mechanism in patients with liver disease. The following parameters were used to indicate the disappearance rate of various dyes from plasma; K for ICG, KAU for 198Au colloid and KRB for 131I-rose bengal. ICG was administered intravenously using three different continuous infusion rates on all patients. The maximum rate of biliary excretion (Tm) as well as the relative hepatic storage capacity (S) were determined. Tm and S definitely decreased in cases with liver cirrhosis. Tm had no relationship to the degree of liver damage, but S fell in proportion to its dysfunction. KAU and KRB significantly decreased in cases of liver cirrhosis, while chronic aggressive hepatitis revealed a marked decrease of Krb without an equivalent decrease of KAU. The correlation coefficient between K and S was definitely higher than that between K and Tm, and K was more closely correlated with KRB than KAU. From these results, it was reasonable to presume that K was more influenced by the hepatic uptake and storage than by the excretion of ICG in the bile, and indicated that the capacity of the liver to handle dyes.


Stereological changes in rat parietal cells after vagotomy and antrectomy. Gastric parietal cells from 44 male adult Sprague-Dawley rats were studied in the electron microscope. The animals were divided into seven groups: normal fasted, normal nonfasted, 4 weeks after vagotomy, 10 weeks after vagotomy and pyloroplasty, 10 weeks after pyloroplasty, 4 weeks after antrectomy, and 10 weeks after antrectomy. Stereological data were obtained from 30 to 40 parietal cells in each animal. In the normal nonfasted rats the parietal cells high up in the glands had a larger secretory surface density than those at deeper levels of the mucosa. Neck parietal cells containing a few mucous granules constituted about 10% of the total number of parietal cells in the normal rats; they were most common in the midgland region. The average parietal cell volume in the normal fasted rats was calculated to be 1100 mu3; the cells were significantly smaller 10 weeks after vagotomy and pyloroplasty and still smaller 10 weeks after antrectomy. In this respect the results after vagotomy and pyloroplasty did not differ from those after pyloroplasty alone. The parietal cell density in the normal fasted rats averaged 144 X 10(3) cells per mm3; in the operated rats (except for the 4-week vagotomized rats) the cells became more numerous. The parietal cell volume density was about equal in all groups of animals, except for the 10-week antrectomized rats, where a significant reduction occurred.


Structural locus of transmucosal albumin efflux in canine ileum. A fluorescent study. This study demonstrates the effects of elevated intestinal venous pressure on the intestinal tissue spaces and the histological locus of the transmucosal albumin flux under such conditions. The authors were able to localize albumin in the tissues using an Evans blue-albumin fluorescence technique. This technique makes use of the fluorescence properties and albumin affinity of Evans blue dye (T-1824). Evans blue dye has a high affinity for albumin and emits a red-orange fluorescence at a wavelength of 720 nm. Evans blue was mixed with a solution of bovine serum albumin at concentrations that yield negligible amounts of free dye. Control ileal samples were obtained in order to visualize the natural tissue morphology and fluorescence. The Evans blue-albumin solution was injected and tissue samples were obtained 15 and 60 min postinjection, then venous outflow was occluded and after 15 and 60 min the tissues were sampled. Each sample was immediately frozen, freeze dried, embedded in paraffin, and 7-mu sections were made. The Evans blue-albumin was demonstrated histologically with a fluorescence microscope. No leakage sites were apparent at normal venous pressures. However, after elevation of venous pressure, Evans blue-albumin was observed in the interepithelial and/or intraepithelial spaces of villus tips, but no Evans blue-albumin was observed either between or within the epithelial cells of the crypts, or within the tubular crypt lumina. These results indicate that at elevated venous pressures, the transmucosal albumin flux occurs exclusively at the villus tip region, suggesting a great vulnerability of the cells found in this region to elevations in tissue pressure as compared to the crypt epithelial cells.


Intestinal adaptation to dietary calcium restriction: in vivo cecal and colonic calcium transport in the rat. Small intestinal calcium transport adapts to dietary calcium restriction, but conservation of calcium by the ileum is incomplete. To examine the role of large intestine in calcium homeostasis, weight-matched growing rats were placed on semisynthetic diets containing 1.2 or 0.02% calcium. After 3 to 4 weeks, net calcium movements in cecum and colon (large bowel excluding cecum and distal rectum) were studied in vivo by perfusing a 0.4, 0.8, or 3.4 mM calcium solution. In animals taking 1.2% calcium, the cecum absorbed calcium actively at 0.8 mM; the colon showed net secretion except at 3.4 mM. In calcium-restricted animals, the cecum absorbed at all concentrations; the colon reduced secretion at 0.4 mM, converted to net absorption at 0.8 mM, and greatly increased net absorption at 3.4 mM. These observations suggest that the large intestine may have a role in calcium homeostasis, particularly when dietary calcium is restricted.


Abnormal regulation of plasma pyridoxal 5'-phosphate in patients with liver disease. Pyridoxal 5'-phosphate (PLP), the coenzyme form of vitamin B6, is essential for many biochemical reactions in the body. Studies in experimental animals have suggested that the liver is a primary site for the formation of PLP circulating in the plasma, and that it may also participate in its degradation. This study evaluates, for the first time, the effects of liver disease in man on the regulation of plasma PLP. The plasma PLP level was measured before and sequentially after the rapid intravenous administration of 50 mg of pyridoxine to patients with alcoholic cirrhosis, acute hepatitis, and extrahepatic obstruction, and to normal control subjects. The base line plasma PLP concentration was significantly lower in cirrhotic patients than in normal persons (P less than 0.025), and there was a tendency for it to be reduced in patients with extrahepatic obstruction. After administration of pyridoxine there was a significant increase in the plasma PLP level over a 2- to 12-hr period, after which the concentration returned gradually toward the initial value. The area under the concentration/time curve was from 2 to 8 times smaller (P less than 0.002) in the patients with liver disease. To assess possible mechanisms of this change, 5 mg of PLP were intravenously administered to the various patient groups and the pharmacokinetics of the disposition were assessed. The initial and steady state volumes of distribution of PLP were comparable in cirrhotics and controls (P greater than 0.05), but the clearance of plasma PLP in cirrhotics was much faster (63.0 +/- 7.4 versus 31.7 +/- 2.7 ml per min, P less than 0.004). Similar findings were obtained in the other liver disease subjects. The in vitro plasma binding of PLP at supracirculatory concentrations was comparable in cirrhotics and controls (99.4 versus 99.5%, P greater than 0.05). (1) plasma PLP regulation in patients with liver disease is abnormal, (2) a significant factor in the decrease in plasma PLP after intravenous pyridoxine administration in these patients appears to be an increase in the total plasma clearance of the coenzyme, and (3) it is postulated that this may be due to increased degradation of PLP by the diseased liver.


Morphometric analysis of rat hepatocytes after total billary obstruction. Using light and electron microscopic morphometric techniques, the effects of 48 hr of extrahepatic biliary obstruction on hepatocyte structure were examined in the rat. Liver cells near the portal area were compared to those in the centrilobular regions of the hepatic lobule. Observations on the normal animals confirm earlier evidence of quantitative differences in the surface density of organelles in hepatocytes located within different regions of the lobule. A striking difference in the quantity of the Golgi complex in the two areas of the lobule was noted for the first time, with the portal cells containing a significantly greater quantity of this organelle than centrolobular hepatocytes. After 48 hr of total obstruction, most of the previously reported qualitative changes in the canalicular and pericanalicular regions were confirmed. Morphometric analysis at the light-microscopic level showed an increase in the number of cells and a decrease in cell size in those cells near the portal area were compared to those in the centrolobular regions of the helar level demonstrated a significant decrease in both rough and smooth surfaced endoplasmic reticulum in cells of both zones, a finding in marked contrast to the hypertrophy of smooth endoplasmic reticulum suggested by other investigators on the basis of qualitative assessments. There was also a striking decrease in the amount of the Golgi complex, limited to cells in the portal regions. In addition, in all zones a decrease in the volume density of mitochondria and lysosomes was noted, whereas the volume of microbodies was increased. It is suggested that this loss in total membrane material within the cell may be secondary to the degranulation and decrease in total surface area of rough surfaced endoplasmic reticulum, an organelle thought to be responsible in part for the synthesis of new cellular membranes. These observations suggest that present concepts concerning the pathogenesis of cholestatic liver disease require reappraisal.


Glucose administration and heme catabolism after caloric restriction. Heme catabolism was monitored through the determination of total serum bilirubin and endogenous production of carbon monoxide in 6 healthy males before and after administration of 100 g of glucose orally and intravenously, respectively. To facilitate comparison, hyperbilirubinemia was induced through a 36-hr period of subtotal caloric restriction before the study. A decrease in production of carbon monoxide was seen after glucose given orally as well as intravenously, whereas total serum bilirubin decreased significantly only after glucose orally. It is suggested that oral as well as intravenous glucose administration temporarily inhibits heme catabolism, at least when given after a period of caloric restriction. In addition, oral glucose might have--probably via a gut-related factor--a facilitating effect on liver uptake of bilirubin.


Bile acid structure and biliary secretion of cholesterol and phospholipid in the cat. The effect of bile acid structure on biliary lipid composition was studied on the anesthetized bile fistula cat. The sodium salts of taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid were infused intravenously in 6 animals in random order in a Latin square design. Bile acids were infused for 2 hr at approximately 270 mumoles per hr; each bile acid period was preceded by a 1-hr infusion of isotonic NaCl. Bile samples from the 2nd hr of bile acid infusion, a period of steady bile acid secretion, were compared, and their bile acid, cholesterol, and phospholipid contents were measured. Mean bile acid secretion rates did not differ among the three bile acids, nor did mean phospholipd secretion rates. In contrast, cholesterol secretion was 3 to 4 times greater with the dihydroxy bile acids than with the trihydroxy bile acid, taurocholic acid. It is concluded that bile acid structure is an important determinant of the lipid composition of bile. Further, this comparison of bile acids has dissociated cholesterol from phospholipid secretion, suggesting that bile acids may influence cholesterol and phospholipid secretion independently.


Intrapancreatic choledochal cyst. Diagnosis by peroral transduodenal cholangiography with description of a new method of surgical treatment. A patient with a choledochal cyst presenting solely with abdominal pain is described. The cyst was diagnosed by endoscopic retrograde cholangiography. The clinical, radiographic, and surgical features of this disorder are briefly reviewed and the need to consider this entity as a possible cause of obscure abdominal pain is stressed.


Detection of a circulating gastric secretagogue in plasma extracts from normogastrinemic patients with acid hypersecretion. Extracts were prepared from plasma of 12 subjects with normal serum gastrin concentration (less than 125 pg/ml), 5 normal subjects and 7 patients with duodenal ulcer and basal gastric acid hypersecretion (greater than 15 mEg/hr). Bioassays of plasma extracts were performed in anesthetized rats with perfused stomachs and acid out-puts were compared with those produced by normal saline and by 50 ng pentagastrin given in random order. Compared with saline, plasma extracts from 5 of 7 hypersecretor patients produced significant stimulation of acid secretion while none of the extracts from normal subjects produced acid stimulation. The stimulant identified in plasma from hypersecretor patients appears to be distinct from gastrin.


Pentagastrin stimulates epithelial cell proliferation in duodenal and colonic crypts in fasted rats. In fasted rats, single injection of pentagastrin (250 mug/kg) stimulates epithelial cell proliferation in the duodenum and colon, but not in the esophagus. Fasting for 64 hours suppresses cell proliferation more markedly in colonic crypts than in duodenal crypts, and pentagastrin restores the cell proliferative activity of the colon and duodenum to levels comparable with those of fed rats. In both duodenal and colonic crypts, differentiating-proliferative cells in the mid-portion of the crypts are more responsive to pentagastrin stimulation than immature proliferative cells at the base of the crypts. Non-dividing epithelial cells are not affected. Pentagastrin has no influence on cell proliferation in fed rats.


Disseminated intravascular coagulation in nonocclusive mesenteric ischemia: the lack of specificity of fibrin thrombi in intestinal infarction. The significance and frequency of fibrin thrombi (FT), the pathological hallmark of disseminated intravascular coagulation (DIC), in ischemic intestine were analyzed in a retrospective study of the infarcted bowel of patients with occlusive mesenteric ischemia (OMI) and nonocclusive mesenteric ischemia (NOMI). Representative intestinal sections were studied from 10 patients with NOMI of the small and/or large bowel and 12 patients, with OMI of varied etiology. Three patients with inflammatory bowel disease and 1 patient with DIC and bowel necrosis were also studied. Routine hematoxylin and eosin stains for fibrin were prepared for each specimen. The number of FT was quantitated. FT were identified in each of the 10 cases of NOMI; however in only 2 were they prominent. FT were identified in 6 of the 12 cases of OMI and in 4 of these 6 they were a prominent feature. Rare FT were present in the cases of inflammatory bowel disease and did not correlate with the inflammatory process. No FT were present in the intestinal sections of the DIC case. FT are a nonspecific feature of necrosis and can be identified in both occlusive and nonocclusive ischemic bowel disease. Their presence in the intestine of NOMI therefore cannot be used to implicate DIC as the primary cause of this entity.


Altered pancreatic function after proximal gastric vagotomy in man. The secretion of bicarbonate into the duodenum in response to stepwise increasing doses of secretin (0.078, 0.23, 0.7, and 2.1 U/kg-hr) was investigated in 11 duodenal ulcer patients before and about 1 1/2 years after proximal gastric vagotomy. After the vagotomy the mean output of bicarbonate in response to the two lowest doses of secretin increased from 2.2 to 3.7 mmoles per 30 min im response to 0.078 U/kg-hr and from 6.6 to 9.8 mmoles per 30 min in response to 0.23 U/kg-hr. On the other hand, the output of bicarbonate in response to the highest dose of secretin decreased from 20.3 mmoles per 30 min before to 16.5 mmoles per 30 min after the vagotomy. The dose of secretin required for half-maximal stimulation decreased from 0.7 to 0.3 U/kg-hr. The calculated maximal bicarbonate response decreased from 27.8 to 17.7 mmoles per 30 min. Thus, increased sensitivity of the bicarbonate-producing cells to low doses of secretin and decreased bicarbonate secretory capacity of the pancreas after proximal gastric vagotomy were found.


A reproducible animal model of acute bleeding ulcer-the "ulcer maker". An instrument has been developed which creates an experimental model of an acute bleeding gastric ulcer. The diameter and depth of these gastric ulcers are reproducible. The instrument can be used endoscopically or at laparotomy. Using this ulcer model nonsurgical modalities for the treatment of upper gastrointestinal bleeding can be compared in a controlled manner. This standard experimental model may also facilitate comparison of results among different research groups.