Vascularization of the pars distalis of the hypophysis in the toad, Bufo bufo (L.) (Amphibia, Anura). A comparative light microscopical and scanning electron microscopical study. I. The vascularization of the pars distalis of the hypophysis of the toad, Bufo bufo (L.), was studied by the traditional method of injecting a mixture of India-ink and gelatine into the circulatory system of the head via the arteria coratis communis. Further, methyl-methacrylate corrosion casts of the brains were made; the hypothalamo-adenohypophysial region of these corrosion casts was studied with the scanning electron microscope. The results showed that the portal vessels which arise from the median eminence do not supply distinct areas in the pars distalis as is supposed by the point-to-point-hypothesis. The portal vessels enter the ventro-median region of the pars distalis and branch off into a three-dimensional network of the secondary capillary plexus of the pars distalis. The plexus is made up mostly by four- to six-sided meshes. This angioarchitecture guarantees an optimal supply of the glandular cells of the pars distalis with nutritional factors and releasing hormones, on the one hand, and facilitates the removal of the hormones which are released by these cells, on the other hand. The venous drainage of the pars distalis is exerted mainly by two large veins, which bilaterally leave  the dorso-lateral region (venous pole) of the pars distalis and by a few small veins, which drain into the wide, sinus-like vessel, which curves around the dorso-caudal region of the pars distalis and joins bilaterally the vena hypophysea transversa.


Vascularization of the pars intermedia of the hypophysis in the toad, , Bufo bufo (L.) (Amphibia, Anura). A comparative light microscopical and scanning electron microscopical study. II. The vascularization of the pars intermedia of the hypophysis of the toad, Bufo bufo (L.) was studied by injection of a mixture of India-ink and gelatine into the circulatory system of the head via the arteria carotis communis. Further methyl-methacrylate corrosion casts of brains were made and the hypophysial region of the corrosion casts was examined with the scanning electron microscope. The results showed that the vascularization of the pars intermedia of the toad hypophysis consists of a single-layered vascular network, which is located on the ventral surface of the pars intermedia. The network is formed by capillaries, which primarily run caudally in a fan-like manner and which show only a few cross-connections. In the rostral region of the pars intermedia this network lies rather superficially, while in the caudal region it slightly penetrates the parenchyma. The vascular network originates from vessels of the neural stalk and from wide capillaries of the rostro-ventral region of the neurointermediate junction. The venous drainage of the pars intermedia is exerted by veins, which leave the caudal region and drain into the veins leaving the venous pole of the pars distalis. The flat, wide meshed vascular net on the ventral side of the pars intermedia, demonstrated in this study, fits into the concept that the pars intermedia of the anuran hypophysis is under the control of nerve fibers coming from the hypothalamus.


The ventricular system in neuroendocrine mechanisms. III. Supraependymal neuronal networks in the primate brain. This investigation has utilized a correlative scanning-transmission electron microscopic technique in the analysis of the primate cerebral ventricular system. This approach has demonstrated a complex network of supraependymal cellular elements upon the walls of the third cerebral ventricle in direct contact with the ventricular lumen. Type I neuronal-like cells and type II histiocytic-like cells with potential phagocytic capabilities have been observed in large numbers throughout the third ventricle. Type I neuron-like cells are discussed in the context that they may represent a population of receptor-cells which serve to assess ambient changes in the composition of bioactive peptides in the cerebrospinal fluid and may serve as a  supraependymal network that integrates the endocrine hypothalamus with other circumventricular organs which may also be sites of neuroendocrine transduction.


Conformational difference in the polar groups of phosphatidylcholine and phosphatidylethanolamine in aqueous phase. Proton and phosphorus nuclear magnetic resonance was used to investigate conformations of o-phosphorylcholine(OPC), o-phosphorylethanolamine(OPE) and L-alpha-glycerophosphorylethanolamine in aqueous solution, and the conformations of dipalmitoyl-3-sn-phosphatidylcholine and phosphatidylethanolamine from E. coli in methanol and chloroform solutions. It has been shown that in every case the O-C-C-N system prefers a gauche conformations, but in the choline moiety the dihedral angle around the C-C bond is distorted from the usual gauche angle, 60 degrees, to a larger one. The dihedral angle of OPC is shown to be more variable than that of OPE. This may be due to the curvature of its potential curve, i.e. asymmetrical curvature around the gauche minima. This property of the phosphatidylcholine molecule may be partly responsible for the flexibility of the phosphatidylcholine bilayer. The coupling is dominant in the P-O-C-C systems of the 5 compounds examined. The results also indicated that the two hydrocarbon chains in phosphatidylcholine or phosphatidylethanolamine are apt to take nearly parallel orientation in methanol solution. This characteristic is favourable for the formation of the bilayer structure.


[Coexistence of neoteny and an internal cycle a polystomatid (Monogenea)]. Metapolystoma cachani a parasite of Ptychadena longirostris (Peters) has been discovered in the Ivory coast. Its life cycle is the first to involve both the possibility of an internal cycle in the bladder of the adult Amphibian and a neotenical reproduction on the gills of the Tadpole. This double process is the link between the Monogeneans which are only parasites of aquatic hosts and those which are adapted to terrestrial hosts. Its place is therefore essential in the phylogeny of Polystomatidae.


[Differences in the sensilla of African and American cercaria of Schistosoma mansoni, the agent of human intestinal bilharziasis]. Schistosoma mansoni parasite of the human intestinal bilharziasis is frequently transmitted in Africa by the Snail Biomphalaria pfeifferi and in America by Biomphalaria glabrata. The comparison between four African strains of cercariae obtained from Biomphalaria pfeifferi and five American strains from Biomphalaria glabrata points out variations in the number and arrangement of the sensory receptors.


[The effect of eating behavior on the circadian rhythm of plasma corticosterone in growing rats]. The circadian rhythm of plasma corticosterone was studied in growing Rats fed on an ad libitum or controlled feeding schedule (six meals per day). Circadian plasma corticosterone rhythm was conventional in ad libitum Rats. Increases of circulating hormone occurred during the last light hours and the first dark hours. Plasma corticosterone rhythm was modified by controlled feeding. Meal feeders exhibited a high value during the last light hours and a secondary hump at midnight. Feeding schedule was not the main synchronizing factor in rat circadian corticosterone rhythm.


[Pituitary control of androgen synthesis in the rat embryo]. Removal of the hypophysis by decapitation of the 19--or 20 days--old Rat embryo is followed by a significant decrease in the ability of the embryonic testis to synthesize testosterone and androstenedione from acetate in vitro. It is concluded that pituitary-testis relationships first appear at 19 days of intrauterine life.


[The presence of para-esophageal bodies in Nematophora Lysiopetalidae (Myriapoda, Diplopoda)]. Demonstration of paraoesophageal bodies presence in the Millipede Nematophora Lysiopetalidae, Callipus foetidissimus (Savi, 1819). As in the Iulidae, Blaniulidae, Strongylosomidae and Glomeridia the paraoesophageal bodies are neurohemal organs having their own secretory cells. Different hypothesies on the origin of secretions in the paraoesophageal bodies of Lysiopetalidae are proposed.


[Cytoplasmic control of cell division in amphibians: changes in the timing of egg cleavage after injection of heterospecific cytoplasm]. Cytoplasm of Xenopus laevis virgin eggs is injected into fertilized eggs of Pleurodeles waltlii, species characterized by an initial development slower than that of Xenopus. The cytoplasm introduced into eggs at the 2 or 4 cell stages accelerates the division of cells in the site of injection, Later on synchronism of cleavage for the different blastomers of operated eggs reappears. The effects of an heterologous cytoplasm on mitosis and endogenic rhythm of cleavage are discussed.


[Scanning microscopy of the early stages of embryonic development of baboons (Papio cynocephalus): oocyte, penetration of the zona pellucida, and morula]. The surface of ovarian oocytes is evenly covered with finger-like microvilli about 1 micron long. Penetration of capcitated spermatozoa in the zona pellucida apparently occurs after acrosome reaction and though a narrow slitmmorulae are constituted of rounded blastomeres, usually of similar size and microvillous covering. A few blastomeres may be smaller than others, probably as a result of faster mitotic rate in one of the blastomeres compared to adjacent ones. Microvilli are numerous in the interblastomeric furrows where junctional ridges are not observed at the 30-40 cell stage.


[Demonstration of a change in the frequency of the characteristic "gonadal atrophy" as a function of the rank of egg-laying in Drosophila melanogaster]. The frequency of gonadic atrophy of Drosophila melanogaster depends on the day of emergence. This variation is related to the rank of egg-laying, the eggs laid down during both first days giving imagoes with a gonadic atrophy more often.


[Presence of a protein disulfide isomerase (EC 5.3.4.1) in wheat germ]. The presence of a protein disulfide isomerase (rearrangease) in wheat embryo has been demonstrated by its ability in reactivating randomly cross-linked ribonuclease. This activity requires a dialysable cofactor; after dialysis, the activity is recovered by addition of reduced glutathione. The enzyme can be precipitated by 70% saturation ammonium sulfate.


[The effects of a heterologous antibody against a crude lipoprotein lipase fraction in mice]. The antigens contained in a crude lipoprotein-lipase fraction from the Rabbit adipose tissue have no effect on Mice, even after daily injections for several months. But they induce an immune reaction in Sheep, allowing one to produce several immune sera with a high physiological activity, without any specific barrier between Rabbit and Mouse. After total absorption of these immune sera by normal Rabbit serum, the remaining antibodies have an activity against esterasic lipoproteins. Small doses of these antibodies induce in Mice marked hyperplastic and degenerative reactions of the adipose tissue and an extensive lysis of the pancreas. A correlative high lymphocytic activation, producing B and T immunoblasts, is induced.


[Trial selection of 2 sub-strains of NZB mice based on the level of chromosome aberrations]. Increased chromosomal breakage is observed in NZB mice. Breeding experiments with mice selected according to breakage frequencies provide evidence that the proportion of animals with high and low breakage figures in the first and second generation progeny depends on the phenotype of the parents.


[The effect of dietary lactose on the ileal absorption of sodium taurocholate in rats]. When Rats were fed a lactose containing diet, both the absorption rate of sodium taurocholate at the level of ileum and the contents of bile acids of the small intestine were increased. On the contrary, feeding of lactose did not modify the daily fecal excretion of bile acids. It therefore appears that dietary lactose increases the intestinal pool of bile acids by increasing their ileal absorption rate and that this effect of lactose is not subordinated to a modification of bile acid synthesis.


[Comparison of the morphogenic effects of JH-I and JH-III during the solitary phase of Locusta migratoria]. After injection of oiled solutions of JH-I metamorphosis was much more disturbed than following the same treatment with JH-III. The two hormones reduced in the same way the mortality which occurred after injection of pure peanut oil in the first hours of a larval stage. JH-1 and JH-III seemed to have the same effect on the two phases of Locusta.


[Inhibition of the reinitiation of meiosis in Xenopus laevis oocytes by three natural antiproteases: antipain, chymostatin, and leupeptin]. Oocytes incubated for 1 hr. in saline containing 1 mg/ml of antipain, leupeptin or chymostatin do not reinstate meiosis when progesterone or ionophore A 23187 are added. On the contrary such oocytes remain able to undergo meiosis when injected with cytoplasm of maturing oocytes (MPF), with Rabbit phosphorylase kinase or with Beef protein kinase. These results demonstrate that the loss of responsiveness to progesterone or ionophore is not due to toxic effects but rather to some interference with a key event which occurs prior to MPF action.


[Immunohistologic study of the chicken kidney]. After absorption with adult Chicken liver homogenate, antisera produced in Rabbits against the DOC-soluble fractions of the sediments obtained after centrifugation of adult Chicken kidney homogenates, react with at least two types of antigens. One, found to be kidney-specific, is localised at the apical part of the cells of the proximal segment of the secretory tubules. The other, also present in the digestive tract, is detectable in the ureter and its derivatives, the collecting tubules by which it seems to be excreted. Despite the lack of organ specificity the latter represents an interesting marker for studying the early steps of the development of the renal collecting system.


[Cell kinetics and experimental rearrangement of daughter chromosomes at the end of mitotic division]. The action of hexamethylene-tetramine (HMT), which causes a late disorientation of the two sets of chromosomes during telophase in Allium sativum L. meristematic root cells, has not been found again, in the same material after synchronization by hydroxyurea. The explanation put forward takes into account the special feature of cells synchronized by chemical methods. Besides, the toxicity of HMT is not the same according to the stage of the cell cycle during the treatment.


[Metabolic activity of goat adipose tissue at the end of gestation and at the beginning of lactation: level of deoxyribouncleic acid content and lipoprotein lipase activity]. In the goat the passage from late pregnancy to early lactation is accompanied by a decrease of the epiploon lipoprotein lipase activity and an increase in the epiploon DNA content. The between-goat variations allow us to emphasize a linear relation between the lipoprotein lipase activity decrease and the reduction of the epiploon volume, expressed on a DNA basis. These parameters, used as indicators of the adipose tissue metabolic status, could contribue to the determination of a feeding strategy adapted to high yield milking Ruminants.


[Fluorimetric assay of 3-o-methyldopamine and 4-0-methyldopamine in rat urine and o-methylation of dopamine]. A new method for the isolation and determination of 3-O-methyldopamine (3 MD) and 4-O-methyldopamine (4 MD) in the urine of Rat has been described. The administration of L-dopa enabled us to detect 4 MD in the urine with a molar ratio 4 MD/3 MD = 0.07. This ratio decreased with the simultaneous treatment of S-adenosylmethionine (SAM). This result might explain the therapeutic L-dopa+SAM in the treatment of parkinsonism, 4 MD being neurotoxic. The low level of 4 MD compared with the level of isovanillic acid, found by other authors, seems to indicate that the 4-O-methylation pathway takes place via dihydroxyphenylacetic acid.


[Response of the brown trout (Salmo trutta, L. 1766) and rainbow trout (Salmo gairdneri Richardson, 1836) to infection by a new rhabdovirus]. Intra peritoneal injection of 200 g Trout hold at + 12 degrees C with 2x10(8) p.f.u. of a new Rhabdovirus (strain 23.75) induces an interferon synthesis within 2 days. (IF titres reaching 2,000 units/ml). 1 month later, the surviving Fish exhibit a specific anti 23.75 neutralizing serum activity (titre 40 to 80) which has been demonstrated to be due to immunoglobulins. This seroneutralization is also recorded in 1/3 of the survivors of natural infection.


[Increase in the non-specific resistance to infection in mice after oral administration of 2 synthetic glycopeptides with adjuvant activity]. Two synthetic glycopeptides (MurNAc-L-Ala-D-isoGln and MurNAc-L-Ala-D-Glu), having adjuvant activity, were shown to enhance non-specific resistance to infection against K. pneumoniae. These compounds were active by various routes including oral administration and even if administered after the challenge. Two steroisomers lacking adjuvant activity did not protect the infected Mice.


[The benthic red alga Ceramium ciliatum var. robustum (J.Ag.) G. Mazoyer is a remarkable biological indicator of littoral mercury pollution]. The study of mercury composition of red Algae Ceranium ciliatum var. robustum, comparatively with other marine organisms and considering its growth and the extent of pollution at various harvesting points: reveals that this seaweed constitutes a conspicuous biological indicator for the littoral mercury pollution.


[Maturation of the female Tetrix undulata (Swrb) (Orthoptera, Tetrigidae): influence of the male and copulation:parthenogenetic egg-laying]. The percentage of laying females and laying time, are compared between mature females (diapause break by chilling) and diapause strain females (diapause not broken by chilling) reared with mature male or diapause male or without male. For the same physiological state of the females (mature or diapause) there is no difference in the percentage of females laying, when they are reared with mature male or with diapause one or none; but the laying time is shortest with mature male, longer with male in diapause, even longer without male. Parthenogenetic egg-pods can be obtain. Rearing with mature males does not break the reproductive diapause of females. In parthenogenetic egg-pods the number of eggs is short for low diapause females; greater for mature ones and greatest for females with strong diapause broken by a corpus allatum implant of mature female of Locusta migratoria. Corpus allatum of the low diapause strain of females of Tetrix undulata have less activity than that of mature females. Few parthenogenetic eggs develop, even less hatch. In Tetrix undulata parthenogenesis is accidental.


[Morphogenesis and hormonogenesis in vitro of granulosa cells of the European badger Meles meles L]. Granulosa cells harvested from follicles of Badger during inactive luteal phaseluteinize in vitro. The results demonstrate that the serum's origin influence progesteron production of Badger's granulosa cells in culture. LH appears equally to be stimulating.


[Existence of cholinergic receptors in the very young chick embryo]. The injection of certain cholinergic agents in the yolk sac of young Chick embryos (40 to 48 hrs. of incubation) gives rise to a twisting of the cervical notochord and spinal cord and contraction of the cervical somites. These morphogenetic changes result in spinal column malformations in older embryos. The effects of the cholinergic agents are inhibited by simultaneous treatments with a cholinergic agonist and an antagonist or a cholinergic receptor ligand. The results lead to the assumption that the early embryos already possess cholinergic receptors, probably located in the notochord.


[Latent differentiation in the endoderm of the young chick embryo]. Initiation and localization of the capacity of self-differentiation in the 1-2 day old chick embryo were studied by means of culturing endoderm fragments, wrapped in a piece of viteline membrane and completely deprived of mesenchyme.


[Use of the method of correspondance analysis to study the pigmentation of the Malagasy migratory cricket during its solitary phase in nature]. The elaboration of an original system of codification and the utilization of the correspondance analysis method makes it possible to draw up an identity card, based on promotal pigmentation, for a natural solitary population of the malagasy migratory Locust. The method leads the way to the study of geographical and temporal variations of the pigmentation.


[Inactivation by 4,6 disubstituted pyrazolo (3,4-d) pyrimidines of the arsenolysis of guanosine by erythrocyte purine nucleoside phosphorylase]. New drugs are proposed in an attempt to reduce the overformation of uric acid in man. The procedure is based on the inhibition of human purine nucleoside phosphorylase selectively investigated in its phosphorolytic sequence. But for technical reasons, analogous inactivation of the enzyme in its comparative guanosine arsenolysis is subject to experimentation.


[Effect of benzatropine on the O-methylation of striatal dopamine]. After treatment by nialamid, benztropine administered to Rats produced an increase in the level of 3-O-methyldopamine in the corpus striatum. It produced a slight increase in the level of striatal dopamine and no change in the level of norepinephrine. The monoamine oxydase and catechol-O-methyltransferase activities of remaining brain showed no variations by benztropine. The results suggest the possible involvement of striatal dopamine and its extraneuronally catabolism in the antiparkinsonian effect of benztropine.


[Partial characterization of the histones of the hepatopancreas and testis of the shrimp Palaemon serratus]. The chromatin of Palaemon serratus hepatopancreas and testes has been isolated. All the classes of histones are present in the fractions studied so far. However, F1 harbors some characteristics different from that of Calf thymus F1. Moreover a supplementary fraction of low molecular weight can be detected in the testes.


[The presence of an endogenous peroxidase activity in hairy cell leukemia cells]. Mononuclear cells from hairy cell leukemia have been studied in three cases by ultrastructural immunocytochemistry. Cells have fairly detectable surface immunoglobulins, without monoclonal distribution however. In addition these cells have a peroxidatic activity which is revealed in the perinuclear space and strands of endoplasmic reticulum.


[Antibody-dependent adherence of peritoneal cells of the rat to Trichinella spiralis larvae]. Washed peritoneal exudate cells from normal Rats firmly adhere to Trichinella spiralis larvae in the presence of serum containing anti-Trichinella antibodies. This effect is observed when muscle larvae, cells and dilutions of anti-sera are incubated for 1 hr. at 37 degrees C. No adherence takes place at 4 degrees C. Whole serum or its gammaglobulin fraction are active and effect is inhibited by the addition of Trichinella antigens. Complement is not essential since antiserum heated for 2 hrs. at 56 degrees C is active. Washed cells from infested animals do not adhere to the larvae in the absence of antiserum.


[Cytochemical analysis of nucleic acid and protein synthesis in fibroblasts treated in vitro by trimethoprim]. Chick embryo fibroblasts cultivated in vitro are treated with trimethoprim. The mitotic activity is strongly depressed. DNA and overall RNA and protein syntheses are inhibited. However, these effects are observed only when the concentration of the drug in the culture medium is relatively high.


[Eyestalk removal and intensive regeneration: joint effects on the molting cycle of Pachygrapsus marmoratus (Crustacea, Decapoda), variability of the critical regeneration stage]. When eyestalk-removal and pereiopod-removal, followed by intensive regeneration, are realized together on the same animal, their accelerative effect on the moulting rate is lower than the effect of only one of these two processes. The critical stage of pereiopod regeneration varies between the moulting stages C4 to D1 according to the physiological state of the Crab.


[Dual activity of the pars intercerebralis of Panstrongylus megisturs (Heteroptera, Reduviidae) in the control of oogenesis and molting]. The action of A and A' cells of the pars intercerebralis of P. megistus on female gonial mitosis and meiosis is established experimentally by selective ablations and by implantations of brains devoid of their A cells. Molting is dependent on two factors originating in each neurosecretory cell type.


[Transcription complexes in subnuclear fractions isolated from mammalian cells: ultrastructural study]. Miller Beatty's technique was adapted to the study of definite chromatin fractions (nucleolar and nonnucleolar chromatin) isolated from Mammalian cells. The ultrastructural organization of the transcriptional complexes obtained depended on the nuclear compartment studied. In isolated nucleoli, there were "Christmas-tree"-like figures. In nonnucleolar chromatin, the figures were different from the former by the internal structure of the RNP fibrils being synthesized.


[Ultrastructural study of the first stages of ovarian post-embryonic differentiation of the paludin Viviparus viviparus L. (Mollusca, Gastropoda, Prosobranch of separate sexes)]. The young Paludin ovary, characterized by its tubular morphology, contains at birth two types of cells: the germinal ones, and others which give later follicular cells. There is no significant cytological difference between the primordial germinal cells of female and male gonad. Among the several cytologic criteria that allow one to distinguish the germinal line from the non germinal one, the most constant is the presence of septate junction between the non germinal cells.


[Somatic and germinal chimerism after the intracoelomic graft of quail splanchnic mesoderm to chick embryos]. The splanchnic mesoderm of the genital area can develop in coelomic graftings as soon as it is colonized by the primordial germ cells (stage 15 of H. and H.). Heterospecific associations between Chick and Quail embryos lead to the differentiation of gonads showing more or less pronounced somatic and germinal chimerisms.


[Lipid content of ischemic bone].

[Lipid content of ischemic bone]. The amount of lipids in fragments of human bones reveals a difference in the composition of the sound and the ill-irrigated parts. Specifying the cause of these variations is rather difficult.


[Synergism between aggregation mutants of Dictyostelium discoideum]. The cells of an aggregateless mutant of Dictyostelium discoïdeum, agip 235, can cooperate with other aggregateless or wild strains to form differentiated aggregates. A soluble mediator liberated by the coaggregating cells seems responsible for the development of agip 235. In most cases, the development of mutant agip 235 stops at the aggregation stage; however, its coaggregation with the mutant 518 results in cosporulation, with the production of viable spores of each genotype, effecting a phenotypic suppression of both mutations.


[Reactivity in vitro of the leukocytes of the earthworm Eisenia foetida Sav. to several mitogenic substances]. Earthworm leukocytes were stimulated by various mitogens including LPS, PHA and Con A. Con A could stimulate leukocytes when they were cultivated in totality. After separation into sub-populations, small-non-adherent-leukocytes and large-adherent ones showed specific reactions with mitogens. Both PHA and LPS reacted with small leukocytes but LPS had no action on large adherent leukocytes.


Contribution of prostaglandins to the renal circulation in conscious, anesthetized, and laparotomized dogs. The effects of an inhibitor of prostaglandin (PG) synthetase, indomethacin, were studied on renal blood flow (RBF) and mean aortic blood pressure (MABP) and related to changes in concentrations of PGs in renal venous blood under widely different experimental conditions. Although levels of PGE-like material ("PGE") in renal venous blood of the chloralose-anesthetized-laparotomized dog were 8-fold greater than in conscious dogs, viz., 0.39 vs. 0.05 ng/ml of blood, respectively, RBF and MABP were similar for each group. Indomethacin in doses as high as 10 mg/kg, iv, affected neither RBF, MABP, nor PG levels either in the conscious dog or in the anesthetized dog. However, in the anesthetized-laparotomized dog, smaller doses of indomethacin (2 mg/kg, iv) decreased RBF by more than 40% and increased MABP by 15%. This was associated with a decline in concentration of renal venous PGs to those levels observed in conscious dogs. The principal renal PG varied according to the experimental conditions. The venous levels of "PGF" were greater than "PGE" in conscious dogs, whereas in acutely stressed dogs the renal venous concentrations of "PGE" were more than 2-fold those of "PGF". Plasma renin activity was highly correlated with "PGE" levels in renal venous blood, but not with "PGF" levels. Thus, in the acutely stressed dog, the renal circulation is supported by a major PG component, withdrawal of which results in a decline in RBF. In contrast, in the conscious dog at rest, renal PGs do not appear to contribute significantly to RBF. The significance of the small basal release of PGs into the renal venous effluent of the conscious dog, which is not affected by indomethacin, remains to be determined.


Triiodothyronine uptake assay with immobilized triiodothyronine antibody as the bound-free separating agent. Available systems for evaluation of degree of unsaturation of thyroxine-binding globulin are hampered at the bound-free separation step. In current assays, inorganic sorbants or ion-exchange resins are used to separate free 125I-labeled triiodothyronine from that bound to thyroxine-binding globulin. The techniques are laborious, time consuming, and not readily adaptable to total automation. In the assay we describe, triiodothyronine antibody, immobilized on the walls of polypropylene test tubes, is used as the bound-free separating agent in the evaluation of degree of unsaturation of thyroxine-binding globulin. The assay is simplified to four steps; washing, centrifugation, and use of columns are eliminated; and the procedure is readily automatable with existing pipetting equipment. Correlation with existing methods is excellent.


Immunochemical determination of human lysozyme by laser nephelometry. The methods currently available for quantitative determination of lysozyme are based on the capacity of the enzyme to lyse Micrococcus lysodeikticus. Previous attempts to develop immunochemical assays have been reported, but the sensitivity was inferior to that of the most widely used lysoplate method. We describe the development of a sensitive immunochemical method for lysozyme assay in which the recently developed laser nephelometer is used. The sensitivity so achieved is at least comparable to that of the lysoplate method, and in some circumstances better. Results obtained by the lysoplate assay and the nephelometric assay correlate well. Among the advantages of our method are easier handling of larger numbers of samples, quicker results, and the possibility of assaying enzymatically inactive forms of the enzyme.


Effect of analytical factors on immunochemical reference limits for complement component C3 in serum of a reference pediatric population. We evaluated analytical factors such as antibody specificity, standard materials, and methodology for the measurement of C3. Mancini-type radial immunodiffusion and immunonephelometry were shown to give comparable data if variables other than procedural variables are eliminated. The most significant analytical factors affecting the measurement were antiserum specificity and source of standard material.


Mechanism of interference by chelating agents and sucrose in radioimmunoassay of angiotensin I. EDTA, 2,3-dimercaptopropanol and sucrose were shown by Scatchard analysis to interfere in the radioimmunoassay of angiotensin I by altering the affinity, but not the capacity, of antibody for antigen. It is stressed that when interfering reagents are present in samples the assay result must be obtained from a standard curve in which each standard contains the interfering reagent(s) at a similar concentration as present in each sample mixture.


A simple automated method for the fluorometric titration of calcium in biological fluids,. A new automatic device has been developed for the determination of the calcium content in biological fluids. The method is based on a fluorometric titration technique, in which calcium is titrated with ethyleneglycolbis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). The end-point of the titration is indicated by quenching of the fluorescence of a calcium-calcein complex, in which calcein is the fluorescein-complexone indicator. To obtain proper results we found it necessary to use a 1 molar potassium hydroxide solution as titration medium. The results are printed out directly in concentration units (mmol/l). In order to carry out these determinations, several electronic and mechanical devices, including a sample-changer, titration cabinet with built-in fluorometer, control unit and electron titrator, were developed. Together they form the new calcium automatic device of which several qualitites such as precision, recovery and correlation have been studied. The disturbing influence of bilirubin has been minimized by using an excitation wavelength of 492 nm, at which there is nearly no absorption by bilirubin. At a concentration of bilirubin of as much as 500 micronmol/l, the recovery of calcium is still about 96%.


The laboratory diagnosis of Sanfilippo disease. The biochemical findings in 29 patients with Sanfilippo disease are reported and a scheme for laboratory diagnosis is outlined. A grossly elevated urinary excretion of heparan sulphate was a consistent and diagnostic finding, even at birth. The excretion of heparan sulphate and chondroitin sulphate was quantitatively similar in types A and B of the condition. Modifications of previously described methods for the determination of heparin sulphamidase in leucocytes or skin fibroblasts and N-acetyl-alpha-D-glucosaminidase in plasma or fibroblasts facilitated the measurement of specific activities. Sanfilippo A disease appeared to be the commonest mucopolysaccharidosis occurring in England and Sanfilippo B disease, one of the rarest forms.


N-Acetyl-beta-hexosaminidase isoenzymes of amniotic fluid and maternal serum. Their relevance to prenatal diagnosis of the GM2 gangliosidoses. The isoenzymes of N-acetyl-beta-hexosaminidase were quantitated in 30 amniotic fluid and 13 maternal serum samples collected between 11 and 40 weeks of gestation using DEAE-Sephadex A-25 chromatography. Isoenzymes A and B consitituted the major components of most amniotic fluids but seven samples characterized by high N-acetyl-beta-hexosaminidase activities contained high proportion of an isoenzyme apparently identical to isoenzyme P of maternal serum. This passage of maternal serum N-acetyl-beta-hexosaminidase into the amniotic cavity could lead to false negative diagnosis  of type B and type O GM2 gangliosidoses if the diagnosis rely solely upon isoenzyme analysis in amniotic fluid. However, the release of maternal enzyme into amniotic fluid seems to be restricted to the third trimester of gestation and should not interfere with prenatal diagnosis of the GM2 gangliosidoses ususally performed at an earlier stage of gestation.


Thyroid-stimulating immunoglobulins in ophthalmic Graves' disease. Thyroid-stimulating immunoglobulins (TSI) have been detected by receptor assay in the sera of 43% of patients with ophthalmic Graves' disease. Comparison of the receptor assay studies with thyroid function tests indicated that in several patients the antibodies detected by receptor assay were biologically inactive. In other patients, thyroid function appeared to be under TSI control with hyperthyroidism prevented by autoimmune destruction of the thyroid.


Hypophosphatemia.

Hypophosphatemia. Hypophosphatemia, with or without phosphorus deficiency, is found commonly in patients with a variety of disease states. Severe hypophosphatemia is most often observed in chronic alcoholics, patients recovering from diabetic ketoacidosis and those being therapeutically re-fed after severe weight loss. Its consequences may be severe. In this review, an attempt is made to examine mechanisms by which hypophosphatemia and phosphorus depletion probably occur, to outline the resulting clinical disturbances and to suggest a plan of treatment.


Atypical manifestations of spinal infections. Because of alarming delays in the diagnosis and treatment of vertebral osteomyelitis we have reviewed our experience over the past 15 years. Of the 36 cases, 25 were pyogenic and 11 tuberculous. Because of late referral there was a delay from onset of symptoms to diagnosis of at least three months in 13 patients. The reason for this was the failure of the initial physician to consider osteomyelitis in the differential diagnosis of a febrile illness associated with back pain. The majority of our patients from the onset did not have intense localized pain, tenderness and a high fever which is the classical clinical picture in this condition. Seven patients with a long history required surgical exploration and debridement of the lesion in order to eradicate the infection. The remainder did well on 6 to 12 weeks of antibiotic therapy. None required spinal fusion. Ten of 11 patients with spinal tuberculosis had curettage of the lesion and spinal fusion. Patients with diabetes, malignancy, alcoholism, corticosteroid therapy and recent lower urinary tract surgery were found to be at particular risk of developing spinal osteomyelitis. Very often it was difficult to identify differences in the presentation of pyogenic and tuberculous infections.


Effect of intra-articular corticosteroids on ligament properties: a biomechanical and histological study in rhesus knees. The effect of intra-articular corticosteroid injections (methylprednisolone acetate) on the mechanical properties of anterior cruciate bone-ligament-bone units was determined. Fifty-one wild rhesus animals provided 88 knee ligaments units that were loaded in tension to failure under fast strain-rate conditions. Alterations in ligament strength and load-elongation properties were found to depend upon corticosteroid dosage and time after injection. Fifteen weeks after the higher drug dosage (methylprednisolone acetate, 6 mg/kg; three injections, spaced weekly) significant decreases occurred in the maximum failure load (20%), energy absorption prior to failure (11%) and linear stiffness (11%) of the ligament unit. In contrast, only minimal non-significant alterations in ligament strength properties occurred at the higher drug usage after 6 weeks in a second group of animals. this strong time-dependence may partially explain the negative findings reported in short term studies. The higher drug dosage used is approximately 10 times an equivalent human dose on a body mass basis and indicates the ability of this class of drugs to significantly alter the mechanical properties of a ligament unity. A third group of animals received a total of two intra-articular coticosteroid injections (single injections spaced two weeks apart) at a dosage (0.6 mg/kg) equivalent to that commonly used clinically in humans. Statistically significant decreases occurred in maximum failure load (9%) and energy absorption (8%); however, this change is believed of little importance to the projected functional capacity of the ligament unit. No detectable systemic effect of the intra-articular corticosteroid injections was found on the mechanical properties of the ligament unit in the extremity opposite to that which received the drug injection. Histological examination after failure showed normal cellularity and staining characteristics of the ligament, fibrocartilage junction and underlying bone. No bone resorptive changes were observed beneath the ligament insertion site. Failure by a ligamentous mode remained the most common mechanism of specimen failure. Scanning Electron Microscopy showed failure of collagen fibers at multiple levels throughout the ligament indicative of a serial pull-apart failure process. A rich supply of vessels to the anterior cruciate ligament was demonstrated and failure of the vessels occured by a necking down process. Insofar as the results apply to humans, they infer the potential for high and frequent doses of intra-articular slightly soluble corticosteroids to produce alterations in ligament strength and function. A single intra-articular injection or one repeated at intervals of several months probably carries little risk to ligament properties.


In vitro mutagenesis assays as predictors of chemical carcinogenesis in mammals. In vitro microbial mutagenesis assays coupled with mammalian activation systems offer promising technique to screen chemicals for their potential carcinogenic activity. The correlation between mutagenic and carcinogenic properties for a large array of chemicals is approximately 0.9. The best correlation exists for those carcinogens which are themselves highly electrophilic or produce electrophilic metabolites. Correlation between mutagenicity and carcinogenicity for hormonal, metallic, or physical carcinogens has been disappointing but not unexpected based on their proposed mechanisms of action. In addition to the application of in vitro mutagenesis techniques to screening chemicals for the identification of potential carcinogens, they are useful tools for investigating genetic, biochemical, and pharmacologic properties of different animal species. Studies with the chemical carcinogen dimethylnitrosamine have been conducted and show a functional relationship between mutagenesis and carcinogenesis. The assays can also be conducted using activation systems prepared from the tissues of any mammalian species. This permits a direct assessment of phylogenic extrapolation by comparing the metabolic activation capabilities of tissues from several mammalian species, including human samples. The advantages of mutagenicity testing are the short period of time required for results, the high sensitivity of the assay (microgram of nanogram quantities of chemicals can be used), and the fact that the ultimate agent can be detected biologically without first necessitating chemical identification and isolation. It appears from current studies that in vitro mutagenesis techniques may well open new avenues of investigation into some old toxicologic problems.


Functional properties of knee ligaments and alterations induced by immobilization: a correlative biomechanical and histological study in primates. The effect of immobility on the biomechanical properties of an anterior cruciate bone-ligament-bone unit of rhesus monkey is reported. Wild primates were used and the captivity time was minimized to lessen disuse changes from cage confinement. The ligament-bone specimens were tested in tension to failure under high strain-rate conditions. After 8-weeks total-body plaster immobilization of the primate, the ligament units showed significant decreases in maximum failure load and energy absorbed to failure (39 per cent and 32 per cent respectively). A dramatic change in ligament load-elongation behavior occurred. There was a statistically significant decrease in stiffness (slope of the load-deformation curve) of the ligament unit which may also be expressed as an increase in ligament compliance (elongation per unit load). The change in mechanical properties following immobility indicated a significant alteration in the projected functional capacity of the ligament unit to resist loading and to resist elongation; factors which relate directly to the ligament's ability to provide joint stability. The mechanisms of failure of the ligament unit, where an increase in osseous avulsion fractures occurred after immobilization correlated with histological changes of bone resorption in the cortex immediately beneath the ligament insertion site. Ultimate failure occurred in many, but not in all specimens, through the weakened bone. This emphasizes the potential for such effects in clinical conditions characterized by reduced bone mass. Alterations in the strength of the cortical bone may affect the integrity of ligament units as a whole. The effect of immobility on ligament units about the knee depended on histological characteristics of the ligament-bone attachment. The anterior cruciate ligament-bond junction, through zones of fibrocartilage, was little affected. In contrast, the tibial insertion of the superficial tibial collateral ligament, directely into bone in relation to the periosteum without well-defined zones of catilage, showed marked interruption after immobility due to bone resorption in the subperiosteal and outer cortical regions. In places the ligament was attached only to the overlying periosteum. In a second and third group of animals, the long-term effects of disuse were investigated. After 5 months' resumed activity following total-body-immobilization, there was only partial recovery in ligament strength although ligament stiffness and compliance parameters had returned to control values. It required up to 12 months for the complete recovery of ligament strength parameters.


Immunochemical characterization and quantitation of the human glomerular basement membrane antigen from the urine of patients with glomerular diseases. A soluble glomerular basement membrane (GBM) antigen was detected in the urines of patients with various glomerular diseases including chronic glomerulonephritis, nephrotic syndrome, chronic renal insufficiency, and lupus nephropathy. The urinary GBM antigen (u-GBM) was immunochemically distinct from other renal antigens and other serum components, but it was cross-reactive with trypsinized human GBM antigen (t-GBM). The molecular size of u-GBM was approximately the same as human serum albumin as estimated by elution patterns on Sephadex G-200. The concentration of u-GBM was estimated quantitatively by a single radial radioimmunodiffusion. Although differed from case to case, a rough correlation with the type and/or stage of nephrotic syndrom existed. It was also demonstrated that the amounts of u-GBM decreased in response to steroid therapy of nephrotic syndrome. It was further shown that in a case of membranoproliferative glomerulonephritis, anti-GBM antibody could be eluted from the kidney removed from the patient. These findings imply that the GBM antigen plays an important role in the pathogenesis of human renal diseases. The pathophysiological significance of urinary GBM excretion in renal diseases is also discussed here.


Chronic ankle "sprain" secondary to anomalous peroneal tendon: a case report. This is an anomaly of the peroneus brevis in a 51-year-old woman that seems not to have been reported previously. Significant functional disability followed a seemingly innocuous ligamentous sprain of the ankle. Persistent ankle pain following minimal trauma should alert the surgeon to the anomalous peroneus brevis symptom complex.


Fatal bilateral pneumothoraces complicating subclavian vein catheterization. Bilateral pneumothoraces complicating attempted bilateral subclavian vein catheterization culminated in the iatrogenic death of the patient. Complications of subclavian vein catheterization are reviewed briefly. This procedure should be limited to patients in whom its use is clearly indicated and should be performed only by individuals who are experienced in the anatomy of the region, who are trained in the technique of subclavian puncture, and who have the means and ability to perform immediate tube thoracostomy should pneumothorax occur.


Unequal distribution of DNA in the macronuclear division of the ciliate Euplotes eurystomus. During asexual fission in the ciliate Euplotes eurystomus, the macronucleus divides amitotically. The macronucleus was found to divide unequally, yielding sister pairs having a mean difference in DNA content of 11.6% DNA content was determined by the Feulgen reaction using a fluorescent Schiff's reagent, and measuring fluorescence by cytophotometry. Variability in macronuclear DNA content was also examined in randomly-paired non-sister cells, and found to be greater than in sister cells. This greater variability could be due to accumulation of differences over a number of divisions, or to interclonal differences in equality of division. Two categories of non-sister cells were examined: recently divided, and "parents" constructed by averaging the DNA contents of progeny. Both showed similar variability in quantity of macronuclear DNA. The fact that cells surviving to divide showed no less variability in amount of DNA than cells immediately after division suggests that extremes in amounts of DNA resulting from unequal division are not selected against.


Genetic dissection of heterochromatin in Drosophila: the role of basal X heterochromatin in meiotic sex chromosome behaviour. We have examined the female meiotic behaviour of three X-chromosomes which have large deletions of the basal heterochromatin in Drosophila melanogaster. We find that most of this heterochromatin can be removed without substantially altering pairing and segregation of the two Xs. To compare the role of heterochromatin in male meiosis we have constructed individuals which carry two extra identical heterochromatic mini X chromosomes. These minis behave as univalents even though their heterochromatin is known to contain satellite DNA. We conclude therefore that this satellite DNA is not sufficient to allow effectively normal meiotic behaviour. In all other respects our results in the male extend and confirm Cooper's postulate that there exist specific pairing sites in the X heterochromatin. Thus we find no support in either female or male meiosis for the concenpt that satellite DNA is involved in meiotic chromosome pairing of either a chiasmate or an achiasmate kind.


Imipramine and children: a review and some speculations about the mechanism of drug action. Although the FDA recommends imipramine hydrochloride (IMI) only for temporary relief of symptoms of enuresis nocturna (EN), the drug has been applied to a number of other pediatric situations, including the Hyperkinetic Syndrome (HS), childhood depression, somnambulism and pavor nocturnus, school phobia, petit mal epilepsy, allergies, autism, encorpresis and head-banging. We have reviewed the literature, with particular attention to the pharmacokinetics of IMI in children, and its putative mechanisms of action. The drug probably works through a number of different actions, and the futher delineation of these will be of considerable heuristic value. We review the toxic effects of IMI treatment and IMI poisoning in children, and the pediatric literature concerning other antidepressant drugs and lithium carbonate (Li).


[Bacterial endocarditis. Clinical picture, treatment and course in 37 patients (author's transl)]. Between March 1971 and April 1976 37 patients were seen with manifest bacterial endocarditis. The main signs were high temperature and cardiac murmurs whereas other "classical" signs such as splenomegaly, anaemia, leucocytosis, and positive anti-streptolysin titres were much less frequent. In 35 cases bacteriological proof was possible. As causative organism a total of 30 gram-positive organisms (of which 15 were Streptococcus viridans and 8 were Staphylococcus species) and 10 gram-negative bacteria (4 of which were Pseudomonas aeruginosa) could be demonstrated. Treatment was mainly with beta-lactam and/or aminoglycoside antibiotics. Use of the combination of penicillin and streptomycin or gentamicin was based on the results of in-vitro bactericidal activity. The main complications were emboli, penicillin allergies, pulmonary involvement and cardiac complications. 13 patients died; the main cause was cardiac failure which was irreversible even despite operative valve replacement during the acute infection in two cases.


The response of newborn sheep to TRH with and without somatostatin. Hormone responses to a bolus injection of thyrotropin releasing hormone (TRH) were studied in 8 newborn lambs between 6 and 19 hours of age. The effect of a bolus injection and 45 min infusion of somatostatin (SRIF) on these responses was studied in 2 other animals. Serial measurements of serum TSH, prolactin, triiodothyronine (T3) and thyroxine (T4) were conducted for 2 to 6 h in all animals. Mean baseline T4 and T3 concentrations were 12.6 microng/dl and 221 ng/dl, respectively, both significantly higher than values in fetal or adult animals. These high values were due to the events of parturition. In spite of the high baseline T4 and T3 levels, there were rapid and significant increases in both TSH and prolactin concentrations in response to TRH alone. The TSH response evoked further increments in serum T3 and T4 concentrations observed at 30 min and 60 min, respectively, both subsequently increasing progressively through 6 h. During the 45 min period of SRIF infusion, the TSH T4 and T3 responses to the zero time TRH injection were minimal. However, after discontinuing SRIF, late increases in TSH, T4 and T3 were observed. The results indicate that the hyperiodothyroninemia characteristic of the newborn period does not block the response to exogenous TRH, whereas the inhibitory effect of exogenous SRIF is observed in the newborn as in the adult. The increased endogenous TRH secretion presumably responsible for the neonatal TSH surge may be overriding the negative feedback effect of thyroid hormones.


Bioassay of circulating luteinizing hormone in the rhesus monkey: comparison with radioimmunoassay during physiological changes. The concentration of biologically active LH in rhesus monkey (Macaca mulatta) serum was measured by a highly sensitive bioassay based upon testosterone production by dispersed rat interstitial cells. The sensitivity of the in vitro bioassay was equal to or higher than that of radioimmunoassay, with detection limits of 0.1 mIU of human menopausal gonadotropin (hMG) or 10 ng of a rhesus pituitary gonadotropin preparation (LER-1909-2). Parallel dose-response curves were obtained for hMG and rhesus monkey pituitary gonadotropin. The method permits bioassy of LH in 20-100 micronl of serum from adult male monkeys, and from female monkeys during the follicular and luteal phases of the menstrual cycle. Bioactive LH concentrations could be assayed in 0.25 to 5 micronl of serum from mid-cycle, postmenopausal, and castrated female monkeys. Serum LH was undetectable in two hypophysectomized adult female monkeys and six intact immature animals, and was 13+/-6 (SD) mIU/ml in adult male monkeys. In adult females, follicular phase LH levels ranged from 17 to 169 mIU/ml, with a mean of 76+/-52 mIU/ml. The midcycle LH peak was 1738+/-742 mIU/ml and the luteal phase values ranged from 6-47 mIU/ml, with a mean of 35+/-5 mIU/ml. Serum LH concentrations ranged from 100 to 900 mIU/ml in two menopausal females, and from 590-1480 mIU/ml in castrated females. Treatment of castrated female monkeys with estrogen plus progesterone produced an initial two-fold rise in serum LH within 3 days, followed by a gradual decline to one-fourth to one-tenth of the initial levels after 10 days of treatment. Serum LH was suppressed to undetectable levels during the third week, and remained so for the duration of the 60-day treatment period. Bioactive serum LH levels were comparable to levels determined by radioimmunoassay during the follicular and luteal phases of the menstrual cycle, with increased bio-immunoratio at the midcycle peak. The concentrations of biologically active serum LH in rhesus monkeys were similar to those in the human female during the follicular and luteal phases of the menstrual cycle, and were higher at midcycle and after castration. Serum LH levels measured by the interstitial cell bioassay in the rhesus monkey showed appropriate physiological changes and responses to gonadal steroid administration. Furthermore, the bioassay did not detect the LH-like material measured by heterologous radioimmunoassay in the serum of hypophysectomized, immature and steroid-suppressed monkeys. Thus, the rat interstitial cell assay provides a sensitive and valid procedure for measurement of biologically active LH in the serum of these non-human primates.


Growth hormone releasing activity of thyrotropin-releasing hormone in rats with hypothalamic lesions. The growth hormone (GH)-releasing effect of thyrotropin-releasing hormone (TRH) was investigated in rats in which central nervous system (CNS)-anterior pituitary (AP) connections had been experimentally interrupted. Sprague-Dawley (SD) female and male rats, underwent bilateral electrolytic lesions in the median eminence (ME) or the ventromedial nuclei (VMN) or were sham-operated (sham-op). Fifteen days after surgery, 0.9% NAACl or TRH was injected iv into sham-op rats or those with lesions in the CNS, anesthetized with urethane, and blood was drawn at 5 and 10 min posttreatment. In the rats with ME lesions, TRH at all the doses used (0.1, 0.4 and 0.8 microng/100 g BW) induced a marked, although not dose-related GH rise, which was not present in sham-op rats after TRH, or after NaCl administration to either rats with ME lesions or sham-op rats. In SD male rats lesioned in the VMN, TRH at doses of 0.4 and 0.8 microng/100 g BW induced significant GH rises, while the lowest TRH dose (0.1 microng/100 g BW) was ineffective; again, TRH was ineffective at all doses used in sham-op rats. Concomitant evaluation of the prolactin (PRL)-releasing effect of TRH (0.1-0.8 microng/100 g BW), showed a striking elevation of plasma PRL in both female and male sham-op controls, but no PRL rise in the rats with ME lesions. The results reveal that in the rat with surgical separation of the anterior pituitary from the CNS, a direct GH-releasing effect of TRH can be obtained, whereas its PRL-releasing effect is no longer observed, and suggest that, by analogy, the GH-releasing effect of TRH present in some disease states of the human may be due to an impairment of CNS-AP connections.


The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer. 4-Hydroxy-f-androstene-3,17-dione (4-OH-A) when tested at various concentrations was found to inhibit markedly the conversion of 4-andorstene-3,17-dione to estrogens inhuman placental and rat ovarian microsomes. To obtain evidence that estrogen biosynthesis could also be reduced in vivo with 4-OH-A, rats were treated sc at a dose level of 50 mg/kg body weight. After 3 h the ovarian veins were cannulated and blood collected. Estradiol concentrations in the plasma were reduced by 80% compared to control values during the proestrous surge and on Day 4 of pregnancy. 4-OH-A was also found to be effective in controlling estrogen-dependent reproductive and neoplastic processes. In rats treated from Day 2-7 of pregnancy, implantation of fertilized ova was completely prevented in some rats, while in others either implantation was delayed or the development of implants was retarded. 4-OH-A treatment of rats having estrogen-dependent breast tumors induced by 7,12-dimethylbenz(a)anthracene caused 80% of the tumors to regress significantly in 4 weeks of treatment; 42% of these regressed completely.


Suppression of feeding and drinking activity in rats following intraventricular injection of thyrotropin releasing hormone (TRH). Since both TRH and somatostatin (SRIF) are localized to the ventromedial hypothalamic nucleus, a region known to be involved in control of food intake, the possibility that these peptides might alter food intake was evaluated. The peptides were dissolved in 0.9% NaCl and injected into the 3d ventricle in a volume of 2 micron1 in animals bearing 3d ventricular cannulae. Food and water had been removed from the cages the night before and the intake was measured at 1 and 6 h after injection. Control injections of 0.15M NaCl or glutathione (3 nmoles) had no effect on food or water intake. At a dose of 3 nmoles, LHRH, SRIF, and TRH suppressed water intake alh. Lowering the dose of LHRH and SRIF to 0.6 nmoles led to loss of this inhibition but the suppressive effect of TRH, which was more pronounced at the higher dose than that of the other two peptides, persisted. Lowering the dose of TRH to 0.3 nmoles led to loss of the inhibitory effect. The dose of 3 nmoles of LHRH did not suppress food intake but this dose of both SRIF and TRH had a significant suppressive effect on food intake at 1 h. There was no suppressive action of a lower dose of 0.6 nmoles of SRIF, but TRH was still effective to suppress food intake at this dose. A dose of 0.3 nmoles of TRH had no effect on food intake. It is suggested that TRH, and possibly SRIF may play a physiological role in control of food intake, perhaps by altering the neural activity within the ventromedial nucleus.


Seizure severity and acquisition and performance of operant tasks in a monkey model. Several studies utilizing an alumina-gel monkey model demonstrated a relationship between degree of epileptic activity and learning difficulty. Three operant tasks were employed: single-unit, gross-motor positive reinforcement, and avoidance conditioning. The data indicated that the number of hours needed to learn any one of the tasks increased with seizure frequency and/or number of EEG interictal bursts. The learning impairment appeared to be a function of the relevance of the required response to the site of the epileptogenic focus.


Epilepsies with astatic seizures of late onset. In 17 patients with a long course of epilepsy astatic seizures became apparent after the age of 14 years. In the patients' childhood astatic seizures had not been observed. The patients suffered from epilepsies with absences and awakening grand mal or psychomotor fits and sleeping grand mal. The EEG revealed spike-wave variant and spike-and-wave complexes as in the Lennox-Gastaut syndrome. Age dependency of Lennox-Gastaut syndrome is discussed. The described type of epilepsy can be understood as a "Lennox-Gastaut syndrome of late onset".


Effect of major motor seizure frequency upon cognitive-intellectual functions in adults. Wechsler Aandult Intelligence Scale and Halstead neuropsychological performances were investigated in three groups of adult subjects with major motor epilepsy classified according to low, moderate, and high seizure frequency. The groups were equated on seizure duration and age at onset variables. On 7 of the 14 psychological measures employed, significant between-group differences were obtained, with poorest, intermediate, and best test scores associated with the high, moderate, and low seizure frequency groups, respectively. Similar performance comparisons were made on two additional groups: a "high risk" group characterized by early onset age, long seizure duration, and high seizure frequency, and a "low risk" group characterized by late onset age, short seizure duration, and low seizure frequency. Highly significant differences were obtained between the high risk and low risk groups on 12 of 14 variables, with the high risk subjects demonstrating severe cognitive and adaptive impairment in comparison to the low risk subjects. The results support the conclusion that increased frequency of major motor seizures is associated with increasing levels of adaptive impairment, and that the probability of severe cognitive-adaptive dysfunction is further and substantially increased when high seizure frequency is accompanied by a history of early onset and long duration of the disorder.


Effect of early versus late onset of major motor epilepsy on cognitive-intellectual performance: further considerations. Two groups of adult patients, one with early (0-5 years), the other with late (10-15 years) age of seizure onset, were compared on 14 variables derived from the Wechsler Adult Intelligence Scale (WAIS) and Halstead's neuropsychological measures. The groups were matched for duration of the disorder and seizure frequency, and all subjects (Ss) had unequivocal histories of major motor seizures. The group with early age of onset obtained significantly lower WAIS, Verbal IQ, Performance IQ, and Full Scale IQ values than the group with late age of onset. No significant intergroup differences were obtained on Halstead's measures, although the performances of both groups were impaired vis-a-vis non-neurological control expectancy. The results suggest that early onset age, as operationally defined in this study, has a specifc differential influence which is restricted to psychometric intellectual functions as measured by the WAIS in groups matched for seizure duration and seizure frequency.


Taurine treatment of spontaneous chronic epilepsy in a cat. Administration of taurine to a cat suffering from naturally occurring chronic (about 3 years) epilepsy caused disappearance of the clinical manifestation of the seizures as well as a marked improvement in the previously grossly abnormal EEG. The treatment consisted of injections of taurine initially, followed by a more prolonged administration of the amino acid by mouth. The combined methods of administration seemed essential for the success of the trial. To date (5 months post-taurine) the animal has suffered only one "grand mal" type seizure which occurred 3 months after the last dose of taurine was administered. Disappearance of the seizures preceded by several weeks the improvement in the EEG. In accordance with previous findings by a number of investigators, the results of this study suggest an immediate depressant action of taurine on hyperexcitable cortical neurons, followed by a more long-lasting, ameliorative influence on cerebral metabolism contributing to an increased resistance to epileptic discharge.


Effect of anticonvulsants on cortical focal seizure in cats. Electrical stimulation of the visual cortex evoked the cortical focal seizure restricted in the neighbor cortex of the stimulated area in gallamine-immobilized cats. The present experiment was performed to clarify the participation of anticonvulsants in the cortex itself. Phenytoin and carbamazepine depressed the focal seizure, as indicated by the shortening of seizure duration and the suppression of spreading. In addition, the high-frequency components in seizure disappeared with the use of these drugs. Phenobarbital and diazepam also shortened the seizure duration. However, the high-frequency components did not disappear although seizure amplitude was depressed. Trimethadione, acetazolamide, and dipropylacetate facilitated the focal seizure. From these results, the participation of the drugs affecting grand mal and partial epilepsies in the cortex is suggested. In addition, this experimental model is though to be useful in elucidating possible modes or mechanisms of anticonvulsant action on cortical neurons by analyzing, after drug administration, the changes in seizure patterns which seem to reflect underlying neuronal changes.


Increased histaminase activity in the atrophic muscle of denervated frog. Sciatic denervation for 1 month in the frog Rana hexadactyla resulted in progressive atrophy of the gastrocnemius muscle without any change in the total DNA content of the whole muscle. Histamine content of the muscle decreased; glutamic and acid content increased and histidine level remained unaltered on denervation. Histaminase activity localized in the muscle decreased; glutamic acid content increased and histidine level remained unaltered on denervation. Histaminase activity localized in the muscle mitochondria increased on denervation. The histidine-degrading enzymes, histidine ammonia lyase, urocanate hydratase and imidazol-5yl lactate dehydrogenase, are localized in the sarcoplasm of the muscle and their activities are not altered on denervation. The histidine decarboxylase activity localized in the mitochondria is not altered on denervation. The reduction in the histamine content of the atrophied muscle may be due to increased mitochondrial histaminase activity but not due to increased decarboxylation of histidine. The loss of 'trophic influence' due to denervation may be manifested in the impairment of mitochondrial histaminase activity.


Purification and comparative properties of the delta and sigma subunits of RNA polymerase from Bacillus subtilis. Bacillus subtilis delta protein is a 21 500-Mr polypeptide that can be isolated in association with RNA polymerase holoenzyme from uninfected bacteria and with modified forms of RNA polymerase from cells infected with phage SP01 [Pero, J., Nelson, J. and Fox, T. (1975) Proc. Natl Acad. Sci. U.S.A. 72,1589]. Although no function has been assigned to delta protein in uninfected cells, this host polypeptide enhances the specificity of transcription by phage-modified forms of RNA polymerase that contain SP01-coded regulatory subunits. This report describes the purification of delta and sigma proteins from uninfected B. subtilis and examines the comparative effects of these polypeptides on transcription by core RNA polymerase. Purified sigma polypeptide was found to stimulate the transcription of phage DNA while having little effect on RNA synthesis with the synthetic DNA poly(dA-dT) as template. In contrast, purified delta protein markedly depressed the transcription of poly(dA-dT) while having little effect on enzyme activity with phage DNA as template. The inhibitory effect of delta protein on poly (dA-dT) transcription was strongly dependent on the presence of KC1 in the RNA synthesis reaction mixture.


RNA sequences in ribonucleoprotein fragments of the complex formed from ribosomal 23-S RNA and ribosomal protein L24 of Escherichia coli. Upon digestion of the complex formed from the 23-S ribosomal RNA and the 50-S ribosomal protein L24 of Escherichia coli, two fragments resistant to ribonuclease were recovered; these fragments contained RNA sections belonging to the 480 nucleotides at the 5' end of 23-S RNA. By determining the sequence of 70% of this latter region we were able to localise the sections which, in the presence of the protein, are resistant to ribonuclease. Our results suggest that the region encompassing the 480 nucleotides starting at the 9th nucleotide from the 5' end of 23-S RNA has a compact tertiary structure, which is stabilised by protein L24.


The "b5-like" domain from chicken-liver sulfite oxidase: a new case of common ancestral origin with liver cytochrome b5 and bakers' yeast cytochrome b2 core. Limited chymotryptic digestion of chicken-liver sulfite oxidase destroys its ability to oxidize sulfite. From the digest can be isolated a heme-binding fragment of molecular weight about 11 000. Its purification is described, as well as its characterization by a number of methods (absorption spectroscopy, circular dichroism, electrophoretic mobility, immunochemical reactivity, amino acid analysis). The heme spectrum shows no detectable difference with that of the native enzyme. The N-terminal sequence of this sulfite oxidase core is reported (34 residues). It shows a strong similarity to that of liver microsomal cytochrome b5 and bakers' yeast cytochrome b2 core. The sequence comparison is discussed in terms of structural similarity to cytochrome b5. Our data suggest a common evolutionary origin for the three b-type cytochromes.


A correlation between glutathione levels and cellular damage in isolated hepatocytes. To obtain high levels of glutathione in isolated hepatocytes an isolation procedure shorter than 16 min was used. This procedure gave a moderately high yield of viable cells (200--300 X 10(6) cells/10 g liver) with 44 +/- 3 nmol of glutathione/10(6) cells. Incubation in Krebs-Henseleit solution containing 2% albumin resulted in a continuous loss of reduced glutathione from the cells, while incubation in a medium containing amino acids and horse serum resulted in increased levels, suggesting active synthesis for 5 h. A short and apparently harmless depletion of reduced glutathione was induced by diethylmaleate or cumene hydroperoxide. A depletion of reduced glutathione lasting more than 1 h was accompanied by an increased cellular leakage. The depletion was induced by either diethylmaleate plus paracetamol or diethylmaleate alone in higher concentrations. A common mechanism for these toxic responses is suggested.


Association kinetics and binding constants of nucleoside triphosphates with G-actin. The dissociation of the complex between 1:N6-ethenoadenosine, 5'-triphosphate (xiATP) and G-actin was initiated by dilution to concentrations between 1 micronM and 5 nM and monitored by the fluorescence change of xiATP. The results were quantitatively explained by a two-step mechanism: a reversible dissociation of the actin-nucleotide complex followed by a fast irreversible inactivation of nucleotide-free G-actin. Under normal conditions (0.8 mM CaCl2, pH 8.2,21 degrees C), the rate-limiting step was the dissociation of the nucleotide-G-actin complex. The half-time of the dissociation of xiATP from G-actin was 290 s as compared to only 13 s for the following denaturation step of nucleotide-free actin. 1 mM EDTA highly accelerated the dissociation step and, regardless of its concentration, the complex dissociated quantitatively within 1 min. Addition of Ca2+ within 20 s after EDTA addition induced a re-association of xiATP with nucleotide-free but still native G-actin. This reversal was kinetically resolved by means of a multimixing stopped-flow apparatus. The association rate constant was 6 X 10(6) M-1s-1. From the association and dissociation rate constant, a value of 2.5 X (10(9) M-1 was calculated for the binding constant of xiATP to G-actin. The binding constant of ATP (1.4 X 10(10) M-1) was derived from the relative binding constant of xiATP and ATP as determined by fluorescence titration of xiATP-G-actin with ATP. These binding constants are 10(3)-10(4) times higher than values reported earlier on the basis of more indirect data.


The molecular defect in a case of (cystathionine beta-synthase)-deficient homocystinuria. 1. Cystathionine beta-synthase activity isolated from fibroblast cultures obtained from the skin of a normal and a homocystinuric individual were both cross-reactive with normal human liver cystathionine beta-synthase antibody. 2. Isoelectric focusing revealed a substantial difference in the isoelectric points of the normal and abnormal fibroblast enzymes. 3. Treatment of purified samples of normal and abnormal fibroblast enzymes with sodium dodecylsulphate followed by polyacrylamide gel electrophoresis indicated that both normal and abnormal enzymes were composed of two sub-units of molecular weights 53000 and 70000. 4. A combination of urea and sodium dodecylsulphate treatment revealed that the respective 53000 molecular weight sub-units were different. 5. It has been concluded that the molecular defect in the case of pyridoxine non-responsive homocystinuria examined in the present investigation arises as a result of an alteration in the structural gene which codes for the lower molecular weight sub-unit of cystathionine beta-synthase.


Thymidine uptake in bacteria: the effect of purine nucleosides. The kinetics of thymidine uptake by Escherichia coli and Bacillus subtilis cells in the presence of adenine and guanine nucleosides was investigated. The initial concentration of thymidine in the growth medium was 0.35 microng/ml while the initial concentration of purine nucleosides ranged from 25 to 250 microng/ml. Adenine nucleosides when present at a concentration more than 50 microng/ml strongly inhibit thymidine uptake by the bacteria. The duration of the inhibition depends on the initial concentration of adenine nucleoside in the growth medium. At an initial concentration of deoxyadenosine (or adenosine) of 250 microng/ml the time of inhibition of thymidine uptake was about 60 min. During this period thymidine is almost completely preserved from the action of bacterial thymidine phosphorylase. Guanine nucleosides (guanosine or deoxyguanosine) do not markedly inhibit thymidine uptake by bacteria even at a concentration of 250 microng/ml. It is shown that they do protect thymidine from the phosphorolytic action of the thymidine phosphorylase although much less effectively than adenine nucleosides. It is suggested that some areas in the bacterial membrane where thymidine phosphorylase is located are not available to guanine nucleosides.


Analysis of the alpha-satellite DNA from African green monkey cells by restriction nucleases. By the use of restriction endonucleases the organization of the alpha-satellite DNA from African green monkey cells (Cercopithecus aethiops) has been analyzed. With endo R-HindIII, endo R-AluI and with endo R-EcoRI at conditions of low salt and high pH (endo R-EcoRI) all of the satellite was digested while only a part of the satellite was cleaved with endo R-Bsu and endo R-EcoRI under standard conditions. With each of the four nucleases a series of fragments was formed which were multiplies in size of a basic repeat unit linked in tandem arrays in the intact satellite. The quantitative evaluation of the digestion with each nuclease as well as with combinations of two nucleases yielded information about the distribution of the cleavage sites. While the arrangement of the endo R-HindIII cleavage sites conforms to a random distribution across the entire satellite, the results from the endo R-Bsu and endo R-EcoRI cleavage patterns are consistent with a picture where the cleavage sites are clustered in fractions of the satellite. Since endo R-AluI recognizes the central four nucleotide pairs of the endo R-HindIII cleavage site, the redigestion of the endo R-HindIII dimer with endo R-AluI gave information about the distribution of mutations in the satellite. The results of these experiments together with the comparison of the sequence divergence determined from digestion with endo R-HindIII and endo R-EcoRI lend support to the hypothesis that mutations have affected all bases in the satellite evenly. The gamma-satellite, another fraction of the African green monkey DNA, could be separated by Ag+/CsSO4 density gradient centrifugation into two components. With the three restriction nucleases used both components gave a background of fragments of heterogenous length on gel electrophoresis with some faint bands of no apparent regularity in one case.


Snake venom toxins. The amino-acid sequences of three toxins (9B, 11 and 12A) from Hemachatus haemachatus (Ringhals) venom. Three toxins (9B, 11 and 12A) were purified from the venom of Hemachtus haemachatus as described previously. Whereas toxin 11 and 12A comprise 61 amino acid residues, toxin 9B contains 63 residues. All three toxins are cross-linked by four intrachain disulphide bridges. The complete amino acid sequences of these toxins have elucidated. The properties of the toxins were compared with those of the cytotoxin group. The toxicities, the sequences and some of the invariant residues of toxin 11 and 12A resemble the corresponding properties of the cytotoxin group. However their immunochemical properties indicate that they are distinct from both the cytotoxin and neurotoxin groups. The sequence of toxin 9B shows that it is related to the cytotoxins, but its toxicity is much lower than those encountered among members of this group.


On the nature of chromophore in pig kidney diamine oxidase. The nature of the 500-nm chromophore in pig kidney diamine oxidase was investigated by absorption spectroscopy and fluorescence in the presence of various chelating or carbonyl-specific reagents. From the spectroscopic measurements the following conclusions can be drawn. First, the 500-nm absorption band is not due to copper, the reduction of which is not related to the disappearance of this band. Second, phenylhydrazine and cycloserine give rise, upon reaction with the enzyme, to absorptions very similar to those of a pyridoxal enzyme, aspartate aminotransferase. Third, these enzyme derivatives are unexpectedly non-fluorescent. Copper removal, obtained after prolonged incubation of cycloserine-treated enzyme in the presence of reducing and chelating agents, leads to a fluorescence similar to that of cycloserine-aspartate transminase. It is proposed that copper is coordinated to the postulated pyridoxal phosphate of diamine oxidase through the pyridine nitrogen.


Computerized transverse axial tomography (CTAT) in the diagnosis of epilepsy. 99 patients with late epilepsy were investigated in our EEG laboratory. In intervals of maximal 100 days (averaged 23 days) a waking EEG recording and a CTAT were carried out. The average age was 43. 62.5% of the pathological CTATs were found in partial seizures with elementary symptomatology. In patients with generalized seizures the diagnosis of symptomatic epilepsy could be made in 20 cases (34%) with the help of computerized tomography. Generalized seizures were related to tumors only in 8.5% in our case material. In 20 of 99 EEGs in our patients there was a continuous delta wave focus, 12 of these with epileptogenic activity. Of these 20 patients, 18 showed a pathological result in computerized tomography. Eight tumors or metastases, 8 cases of atrophy (7 local and 1 diffuse) as well as 1 case of encephalitis could be diagnosed. 12 EEGs showed continuous or intermittent theta wave foci. Computerized tomography never gave a pathological finding in these patients. If one compares the results of CTAT and EEG in cases of tumor, the agreement between positive tomography and the pathological EEG is very high (97%): 33 positive CTATs comapred with 31 positive EEGs. Our investigations with computerized tomography show organic findings in 34 of 99 epilepsies, that is about 34%.


Metabolic and clinical studies on patients with acromegaly treated with bromocriptine over 22 months. In twenty-two patients with active acromegaly who were untreated or unsuccessfully operated or irradiated (mean growth hormone (GH) values greater than 4 ng/ml) the following investigations were performed: routine laboratory tests, tomography of pituitary fossa, oral glucose tolerance tests, TRH and other pituitary function tests and GH profiles over 5-10 h before and during bromocriptine treatment with daily doses between 7.5 and 50 mg. In seventeen patients GH was suppressed to less than 50% by bromocriptine, in thirteen of them it was normalized on at least one occasion. A TRH induced GH release was observed in all but two responders to bromocriptine before therapy. This effect of TRH was not blunted during treatment with bromocriptine and also in the two patients with negative tests before therapy a significant GH increase was observed. In no non-responder to bromocriptine was a significant increase of GH after TRH observed. One patient showed a secondary resistance to bromocriptine during a period of treatment with griseofulvin. In the remaining sixteen patients the GH suppression has been consistent for between 3 and 22 months. A single dose of pimozide abolished the bromocriptine effect on GH totally in one patient; in others a slight or no significant effect was observed. Tissue swelling and sweating decreased in all bromocriptine responders and glucose tolerance improved in five patients. In four diabetic patients a partial or full remission of diabetes occurred. Apart from postural hypotension after the first administration in two patients no other severe side effects have been observed. Sella size and the other pituitary functions did not change during the time of the study. It seems that a high percentage of acromegalics may be successfully treated with bromocriptine.


Blood pressure in subjects with hypercalcaemia and primary hyperparathyroidism detected in a health screening programme. Primary hyperparathyroidism was the most likely diagnosis in sixty-eight non-thiazide treated patients with hypercalcaemia detected in a health screening. The group included fifty-five females and thirteen males with a mean +/- SEM age of 55.0 +/- 0.7 years. On a pair basis, these patients were compared with a series of sixty-eight age- and sex-matched normocalcaemic subjects selected from the health screening register. Five subjects in each group were receiving medication for hypertension. Systolic and diastolic blood pressures were significantly higher in the hypercalcaemic subjects in the remaining fifty-eight pairs (P less than 0.001). This difference was unrelated to impaired renal filtration and many other factors associated with hypertension. It is concluded that hypercalcaemia and/or other effects of deranged parathyroid function per se may result in a blood pressure elevation on which need not necessarily attain the level of hypertension.


Immunoglobulins in myasthenia gravis: effect of human lymph IgG 3 and F (ab')2 fragments on a cholinergic receptor preparation from Torpedo marmorata. Lymph IgG from patients with myasthenia gravis was shown to inhibit the binding of radio-labelled Naja naja siamensis alpha-neurotoxin to membrane fragments from the electric organ of Torpedo marmorata. This effect could be related to IgG subclass 3 and to the F(ab')2 fragment. These findings confirm the involvement of antibodies of postsynaptic structures in myasthenia gravis.


Effects of parathyroid hormone on total protein, calcium magnesium, phosphorus, sodium and potassium concentrations of normal human parotid saliva. The effects of parathyroid hormone (PTH) administered to six young normal adult subjects on protein, calcium, magnesium, phosphorus, sodium and potassium concentrations in parotid saliva have been studied in relation to the salivary flow rate. Stensen's duct was cannulated and excretion patterns of the constituents determined before and after stimulation of saliva production by lemon juice. After a control period (period 1), 50 U of PTH were given i.v. followed by an infusion of 2 U/min for 60-90 min (period 2). In the absence of any detectable changes in plasma, PTH induced a significant rise of salivary protein, calcium, and phosphorus concentrations at rest and following lemon juice stimulation, and of sodium concentration, but only at high flow rates for the latter. PTH did not change magnesium and potassium excretions significantly. Control experiments without PTH were performed on five other subjects. Protein, phosphorus and potassium concentrations did not change significantly between period 1 and period 2. Calcium and sodium excretions were reduced and magnesium excretion increased during period 2. These results provide evidence that PTH acts on the parotid gland by affecting protein secretion and electrolyte transport. Possible mechanisms of these changes are discussed.


Sex differences in serum lipids and lipoproteins at birth. In a study of 1426 males and 1391 females at birth the mean concentrations of cholesterol in total serum, in the sum of very low density and low density lipoproteins and in high density lipoprotein were significantly higher in females than in males. No sex difference was present in the concentration of triglycerides either in total serum or in the lipoprotein fractions.


Bile acid metabolism in ileostomy patients. In ten ileostomy patients, a 14C-cholylglycine breath test was performed. The 14CO2 in the exhaled air and the 14C bile acid quantity and composition and fat content in the subsequent 24 h ileostomy effluent were determined and compared to the values in twenty healthy controls. The results show that in ileostomy patients only minor bile acid-deconjugation occurs in vivo. Deconjugation in the ileostomy bags was found to be mainly responsible for the absence of conjugated bile acids in many of the ileostomy effluent samples. Secondary bile acids were not present in these patients, as determined by TLC. The fecal fat and bile acid excretion was found to be in the normal range in ileostomy patients provided no concomitant ileum resection was present.


Pituitary-testicular function in acromegalic and hypophysectomized patients. Serum testosterone, LH, and FSH before and after i.v. injection of LHRH were studied in ten acromegalic men and in twenty-one males after hypophysectomy. Controls were normal men matched according to age. Compared to the controls, basal FSH was slightly higher and basal LGH slightly lower in the untreated acromegalics. The differences were not statistically significant. Serum testosterone and the ratio between basal FSH and LH were significantly lower in the patients. Following hypophysectomy because of acromegaly, the values were essentially unchanged. Hypophysectomy because of a functionless chromophobe adenoma resulted in a significantly lower maximum value of LH but not of FSH after LHRH. The results show that hypogonadism in acromegaly might be a result of imbalance between LH and FSH. They furthermore demonstrate that testing the pituitary-testicular function with LHRH in patients with pituitary disorders seems to be of limited value.


Influence of sex, testicular development and liver function on the bioavailability of oral testosterone. The bioavailability of orally administered testosterone was investigated in normal and hypogonadal men, prepubertal boys, normal women, and in patients with fatty liver, liver cirrhosis and surgical portocaval shunts. Peripheral testosterone concentrations remained unchanged in normal men and men with fatty liver, whereas a steep increase was observed in all other groups. The greatest increase was seen in patients with compensated liver cirrhosis and with portocaval shunts. The steep increase of peripheral testosterone in boys, women and hypogonadal men is attributed to their having a lower activity of androgen-metabolizing liver enzymes than normal men. The increase in patients with cirrhosis is most likely caused by intra- and extra-hepatic portocaval shunts.


Treatment of experimental murine amyloidosis with dimethyl sulfoxide. Dimethyl sulfoxide was administered intravenously for 60 days to twenty mice with casein-induced amyloidosis. Partial or total disappearance of amyloid deposits occurred in all treated animals. The urine of these animals contained a substance from which amyloid fibrils could be synthesized. A control group of mice with casein-induced amyloidosis given saline injections showed massive amyloid deposition in the liver and in the spleen at the end of the experiment. Neither the urine of these mice nor the urine of normal control mice treated with dimethyl sulfoxide contained substances from which amyloid fibrils could be synthesized. It is our assumption that dimethyl sulfoxide treatment of mice with amyloidosis resulted in a break up of amyloid fibres into small subunits which were excreted in the urine.


Motility- and blood flow-dependent absorption of amino acids in canine small intestine. A relationship between L-phenylalanine and L-serine absorption, intestinal motility and blood flow has been studied with a canine in situ isolated jejunal loop in acute experiments and in chronic preparations in conscious dogs. During spontaneous rhythmic contractions, as well as after mechanical and pharmacological stimuli, rhythmic changes in blood flow, related to intestinal contractions, were observed. They had no bearing on mean blood flow or absorption as long as they did not occur together with tonic contractions. The tonic contractions resulted in a prolonged decrease in jejunal blood flow ano diminished amino acid absorption rate. Absorption and motility index, as well as blood flow and motility were negatively correlated. There was a positive rectlinear correlation between intestinal blood flow and absorption, regardless of whether changes in blood flow resulted from the increase in motility or were induced by intestinal artery occlusion. These correlations suggest that changes in amino acid absorption during increased motility depend on changes in blood flow. This relationship may be important in clinical syndromes with hypermotility.


The permeability of the blood-brain barrier during electrically induced seizures in man. The blood-brain barrier (BBB) in man was studied during various conditions using the indicator dilution method of Crone [8]. Using 113m In-DTPA as reference substance the extraction, E, of the small test substances 24Na+, 36Cl-, 14C-urea and 14C-thiourea was estimated from the areas under the venous outflow curves following intracarotid slug injection of tracers. Interlaminar diffusion and red cell carriage were taken into consideration when calculating E. Cerebral blood flow (CBF) was measured using the intra-arterial 133Xe-injection method. Twenty-two patients receiving electroconvulsive therapy (ECT) were studied before and during seizures and during hypercapnia. Before seizures the extraction values in % were as follows: ENa+ 1.6, ECl- 1.9, Eurea 3.9 and Ethiourea 7.8; the corresponding values for the permeability-surface area products (PS) in ml/100 g x min were 0.5, 0.3, 0.7, 4.1, respectively. During seizure a decrease of Ethiourea and an increase of PSurea were significant. During hypercapnia PSNa and PSthiourea rose significantly. Due to the similarity of the findings in those two high flow situations it is suggested that the changes of CBF and not the epileptic activity are responsible for the changes in permeability. The mechanism of action may be a stretching of endothelial cells in the cerebral vessels or an opening up of new capillaries, or a combination of both.


Blood-brain barrier during electroshock seizures in the rat. The effect of electrically induced seizures on the permeability of the rat blood-brain barrier was investigated. The small radioactive tracers sodium (24Na+), chloride (36Cl-) carbon labelled thiourea (14C-thiourea) and glucose (14C-D-glucose) were studied in indicator dilution experiments with indium labelled diethylenetriaminepenta-acetic acid (113mIn-DTPA) as reference substance. This method allows a quantitative estimate of the transcapillary loss of solutes, the extraction (E), during a single passage through the brain. Passage of macromolecules was studied using as marker substance Evans Blue which binds to plasma albumin. In the resting state ENa, ECl, Ethiourea and Eglucose were 2.9, 4.8, 9.3 and 12.5%, respectively. During seizures and during shortlasting hypercapnia E glucose decreased while E for the other tracers was unchanged. As cerebral blood flow increased, there must be an increased transfer of test substances into the brain. This finding is in agreement with recent human studies [15]. When Evans Blue was injected intravenously prior to electroshock, there was no staining of brain tissue after one electroshock but following repeated electroshocks some staining was observed. In an attempt quantify this transcapillary loss of albumin by means of indicator dilution, 51Cr-labelled erythrocytes were used as intravascular reference substance against 113mIn-DTPA (a plasma tracer). However, the albumin loss (by pinocytosis or otherwise) occurring after ten electroshocks could not be detected during a single passage through the brain.


[Changes of the uterine size during pregnancy in cynomolgus monkeys (Macaca fascicularis) (author's transl)]. This paper describes changes in the uterine size during the normal course of pregnancy in cynomolgus monkeys. Twenty-four females which had conceived by 3-day individual mating with a male were laparotomized 4,5,6,7,8,9,10,15 and 20 weeks after conception. The width, thickness and length of uterus were measured by a pair of callipers. Them, the uterine volume was estimated by the formula, V = 4/3 piab2 (a, b: uterine length x 1/2, uterine width x 1/2). The increase in the uterine width (y) during pregnancy could be expressed as a linear equation: y = 0.35x + 1.48 (x: weeks after conception). The thickness of pregnant uteri could be represented by a a linear equation: y = 0.36x + 1.40. From the 4th to the 20th week of pregnancy, the uterine length increased along a straight line expressed as a linear equation: y = 0.58x + 1.14. Except for nonpregnant uteri, the change in the uterine volume after pregnancy could be expressed as a linear logarithmic equation: log y = 2.319 log x -0.315. These 24 pregnant monkeys had followed the normal course of gestation until the time of laparotomy without any abnormality in their fetuses of their placentas, indicating that the values obtained throughout this study are of practical use for taking care of pregnant cynomolgus monkeys.


Pulvinar-latero posterior afferents to cortical area 7 in monkeys demonstrated by horseradish peroxidase tracing technique. Pulvinar-latero posterior afferents to the parietal cortical area 7 of the monkey have been demonstrated by means of horseradish peroxidase (HRP) tracing technique. Following HRP injection of area 7, labelled neurons have been found in the pulvinar medialis and the nucleus lateralis posterior. The role of these pulvinar projection fibers is discussed with reference to the "visual neurons" of area 7 recently recorded from.


Neuronal activity in the vestibular nuclei of the alert monkey during vestibular and optokinetic stimulation. Recordings from neurons of the vestibular nuclei were performed in  alert monkeys. Type I and type II units were identified by rotating the monkey about a vertical axis. Al neurons responded also when only the visual surround was rotated around the stationary monkey. The combination of visual and vestibular stimulation points towards non-algebraic summation characteristics for the two inputs, with each input dominating the response over a certain range.


Stimulus- and response-dependent units from the occipital and temporal lobes of the unanaesthetized monkey performing learnt visual tasks. 43% of units recorded from the foveal prestriate cortex, inferotemporal cortex or amygdala of 15 rhesus monkeys performing visual discrimination or serial reversal tasks were responsive to all or some visual stimuli or other aspects of the task. Six units showed activity during movements required for performance of the task. It was not possible to determine whether unit activity could be related to the learnt association of the visual stimuli with reward.