[An experimental and clinical study of the effect of ketotifen in the treatment of extrinsic bronchial asthma (author's transl)]. The therapeutic value of ketotifen (Zaditen), a new anti-allergic drug, was studied in patients with extrinsic bronchial asthma. a) In 8 persons the protective effect on bronchial provocation tests with allergen was examined 3 and 14 days after treatment and compared with cromoglycate (Intal); b) 19 patients were treated for 6 months with 2 x 1 milligram ketotifen (n = 7), 2 x 2 mg ketotifen (n = 7), 2 x 1 mg clemastine (Tavegil) (n = 5). The results were as follows: a) The amount of inhaled allergen causing a fall of 20% in FEV1.0/VC was 9-12 times larger with both therapeutic regimens. b) Ketotifen definitely improved the asthmatic symptoms as compared with clemastine. The improvement was independent of the dosage. Side-effects occurred more frequently with clemastine. The study confirms the in vitro demonstrated anti-analphylactic properties of ketotifen; that it can be taken by mouth is of particular clinical interest.


[Autoimmune diseases in the lungs and pleura (author's transl)]. Diseases of autoaggression can be produced if immunotolerance to endogenous tissue is lost. Such diseases become manifest in the pulmonary and pleura regions mainly within the framework of systemic diseases of the connective tissue (collagenoses) and of the vessels (angiitides). Lupus erythematodes disseminatus belongs to the first group which also includes rheumatoid arthritis, sclerodermia, and dermatomyositis, whereas panarteritis nodosa belongs to the second group, which comprises among others arteritis of the arteria pulmonalis, Wegener's granulomatosis, Goodpasture's syndrome and Ceelen's disease. Pleuropulmonary involvement is frequent in these systemic diseases; it is in fact the principal sign in Goodpasture's syndrome and in Ceelen's disease.


[L-asparatic acid synthesis from ammonium fumarate by free and immobilized Escherichia coli cells]. E. coli 85 cells with a high aspartate-ammonia-lyase activity were immobilized through polyacrylamide gel incorporation. Proper conditions to assay aspartase activity of E. coli cells were developed. Kinetic patterns of aspartate-ammonia-lyase reaction catalyzed by free and immobilized E. coli 85 cells were studied. The synthesis of L-aspartic acid from ammonium fumarate had the following characteristics: specific activity of (4--6) . 10(-5) mmole/mg.sec for free cells and (6--8) . 10(-5) mmole/mg.sec for immobilized cells with their content in polyacrylamide gel of 5--10 mg protein per g wet gelm pH 8.3--10.0.


[Polarographic method of determining formaldehyde in air]. A rapid polarographic method for determination of formaldehyde microconcentrations in air has been developed. The method is highly sensitive - 0,5 cg/ml, which is 10 times higher than the sensitivity of the known methods now at use, with standard deviation less than 1.0. It is formaldehyde-selective - other saturated and unsaturated aldehydes, ketones, phenol, furfurol etc. do not interfere the determination. Sampling takes 15-20 min, polarographic analysis - 1 to 2 min. The method has been tested under conditions of production and proved to be highly reproducible and comparable with the colorimetric chromotropic acid technique.


[Dynamics of nisin accumulation in a culture of Streptococcus lactis]. The dynamics of nisine accumulation by its producer Streptococcus lactis, str. MSU was studied. In the course of the producer cultivation on the liquid nutrient medium there was a correlation between total, cellular and filtrate nysine. The content of cellular nysine increased gradually to reach maximum by the 6th day of the strain cultivation. The content of filtrate nisine reached maximum on the 2nd day and declined two-fold by the 7th day of cultivation.


[Effect of alpha and beta receptor blockaders on the degree of glycemia, growth hormone content of blood and catecholamine excretion in insulin-dependent diabetes mellitus]. Glycemia, growth hormone level and urinary catecholamine excretion were studied in 182 patients suffering from insulin-dependent diabetes mellitus during insulin therapy alone, and in 33 during treatment with insulin plus alpha- and beta-adrenoblockers. Under the effect of alpha-adrenoblockers glycemia proved to fall in the insulin-dependent patients, without increasing the insulin dose. The STH level diminished in these patients under the effect of alpha-adrenoblockers, even when glycemia persisted at the same level. But beta-adrenoblockers aggravated decompensation and the STH level remained unchanged. alpha and beta-adrenoblockers decreased the urinary adrenaline excretion and elevated noradrenaline, dophamine and DOPA excretion, irrespective of blood glycemia. The authors recommend the use of alpha-adrenoblockers to prevent the necessity of a considerable elevation of insulin doses during compensation in patients with the insulin-resistant form of diabetes mellitus. beta-adrenoblockers are not recommended in diabetes mellitus.


Reactions of cysteamine and other amine metabolites with glyoxylate and oxygen catalyzed by mammalian D-amino acid oxidase. Pig kidney D-amino acid oxidase [D-amino-acid:oxygen oxidoreductase (deaminating), EC 1.4.3.3] catalyzes a rapid uptake of oxygen when high concentrations (50-100 mM) of glyoxylate and the following amines are present under usual assay conditions (pH 8.3): cysteamine, 2-aminoethanol, putrescine, D,L-1-amino-2-propanol, D,L-2-amino-1-propanol, 3-amino-1-propanol, D,L-octopamine, ethylenediamine, and L-cysteine ethyl ester. Notable physiological amines that do not support a rapid O2 reaction under the above conditions include histamine, serotonin, epinephrine, norepinephrine, spermidine, spermine, and cadaverine. A more detailed kinetic investigation of the reactions involving the first four reactive amines listed above indicated that the cysteamine reaction proceeds at a rapid rate even when cysteamine and glyoxylate are present at less than millimolar concentrations, but greater than millimolar concentrations are needed in the other amine reactions in order to observe a reasonable rate. At low concentrations and pH 7.4, the cysteamine-glyoxylate substrate (presumably thiazolidine-2-carboxylic acid) reacts an order of magnitude faster than any other known D-amino acid oxidase substrate. Considerable circumstantial evidence suggests that the reaction involving cysteamine is occurring physiologically, but the reactions of other amines would be occurring in the cell at a very low rate, if at all. It is proposed that the product of the enzymic reaction may be a metabolic effector that can modify the reactivity of proteins or nucleic acids by covalent attachment.


[Change in the lactotropic function of the adenohypophysis and the system of its regulation in rats after thyroidectomy]. The prolaction content in the adenohypophysis decreased more than two-fold, and its biosynthesis and release were significantly intensified in deficiency of thyroid hormones. The study of the hypothalamus and epiphysis links controlling the lactotropic function of the hypophysis demonstrated that the biosynthesis and release of prolactin were not inhibited after thyroidectomy. On the 13th--14th postoperative day no irreversible changes were revealed in the hypothalamic links of the control of this function, since it responded to prolactin administration to the experimental animals.


Increased levels of adenosine 3',5'-cyclic monophosphate in Tetrahymena stimulated by glucose and mediated by Ca2+ and epinephrine. Stationary phase Tetrahymena cells exposed to 0.5-1% glucose experience an 8-fold increase in intracellular cyclic AMP within 1 hr. The increase follows an enhanced uptake of Ca2+ triggered by the glucose addition. Inhibiting the Ca2+ influx with ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid blocks the increase in cyclic AMP, but the block can be reversed by the addition of epinephrine. Both this epinephrine effect and the glucose-induced increase in cyclic AMP are counteracted by the beta-adrenergic inhibitor dichloroisoproterenol.


Conversion of glutathione to glutathione disulfide by cell membrane-bound oxidase activity. An apparently specific glutathione oxidase activity is present in renal cortex, epididymal caput, jejunal villus tip cells, choroid plexus, and retina (but not in liver). The activity is membrane-bound and is localized on the luminal surface of the brush border membranes of the kidney and jejunum. The distribution and localization of the oxidase are similar to those of gamma-glutamyl transpeptidase, suggesting that there is a significant relationship among the translocation of intracellular glutathione, the extracellular oxidation of glutathione to glutathione disulfide, and the reactions of the gamma-glutamyl cycle. Thus, both glutathione present in the blood plasma and intracellular glutathione translocated to the cell surface are accessible to oxidation and transpeptidation. Acceptor substrates of the transpeptidase (e.g., L amino acids) promote transpeptidation and decrease oxidation of glutathione. Conversion of glutathione to glutathione disulfide is followed by utilization of the latter compound by gamma-glutamyl transpeptidase and dipeptidase. Although intracellular oxidation of glutathione to glutathione disulfide is readily reversed by the action of glutathione reductase, glutathione disulfide formed extracellularly cannot be reduced; instead, it undergoes hydrolytic and transpeptidation reactions leading to gamma-glutamyl amino acid and amino acid products which may be recovered by being transported into the cell.


Mitrochondrial NADH dehydrogenase in cystic fibrosis. We have shown that skin fibroblast from patients with cystic fibrosis (CF) and from carriers for CF [heterozygotes (HZ)] consume more O2 than do their controls. When the mitochondrial electron transport inhibitor rotenone was added to the cells, the relative inhibition of O2 consumption was CF greater than HZ greater than controls (P less than 0.005 in both comparisons). Because rotenone specifically inhibits NADH dehydrogenase, [NADH: (acceptor) oxidoreductase, EC 1.6.99.3], which is the enzyme of energy-conserving site 1 of the mitochondrial electron transport system, activity and kinetics of this enzyme system were studied in fibroblast homogenates. NADH dehydrogenase activity was equal in cells from the three genotypes. At pH 8.0, affinity of the enzyme for its substrate was CF greater than HZ = controls; at pH 8.6, affinity was CF greater than HZ = controls (P less than 0.005 for the differences). pH optima for the genotypes were without exception 8.6 (CF), 8.3 (HZ), and 8.0 (control). HZ and control lines were distinguished unequivocally in a blind test on the basis of differences in pH optima. Purified mitochondrial preparations revealed pH optima identical to those found in whole cell homogenates. These data suggest that the mutant gene responsible for CF is expressed in the complex mitochondrial NADH dehydrogenase system.


Exocytotic shedding and glial uptake of photoreceptor membrane by a salticid spider. Receptors in the anterior lateral eyes of salticid spiders possess paired rhabdomeres. The tips of the rhabdomeral microvilli lie adjacent to non-pigmented glial processes. Photoreceptor membrane is lost during turnover by a hitherto undescribed process: individual microvilli lengthen at their tips, taper, and are received by corresponding, coated endocytotic pits in the glial membrane. Pits detach as coated vesicles with coherent fragments of microvilli within them, lose their coats, and accumulate in the glial processes as disorderly membranous detritus. Some microvillus membrane disintegrates before local endocytosis, and appears to get into the glial arms distant from the parent rhabdomere by invaginations which are either endocytotic clefts or a tubulo-cisternal system, but whose precise nature is not yet clear. No photoreceptor membrane is lost by pinocytosis into the receptor cytoplasm. Analogies between the behaviour of this system and the phagocytosis of shed vertebrate photoreceptor membrane are briefly discussed.


Structure and histogenesis of tooth plates in Sagenodus inaequalis Owen considered in relation to the phylogeny of post-Devonian dipnoans. The histology of tooth plates of Sagenodus inaequalis has been investigated to obtain information on the histogenesis of the tissue. The histological mechanisms of growth and replacement of the tooth plate are described in terms of an increase in area of the tooth plate by addition of denticles to the lateral margins of the ridges, replacement of worn dentine at the tritoral surface by basal growth of dentine and invasive growth of dentine into the surrounding bone at the anterior and medial margins. The histogenesis of a specialized character for dipnoans is described, namely hypermineralized dentine, or petrodentine, within the tooth plates. This has placed an advanced character further back in the phylogenetic organization of dipnoans than was previously recognized. The implications of these observations are discussed in relation to proposed phylogenies and previous observations on tooth plates of other dipnoans. It is concluded that Sagenodus inaequalis shared a common ancestor with both the ceratondontids and the lepidosirenids. A sequence is proposed for the phyletic relationship of tooth plate-bearing dipnoans. From a consideration of the features of histogenesis of this specialized dentine, the alternative terminologies are reviewed and petrodentine (Lison 1941) chosen for the hypermineralized dentine and syndentine (Thomasset 1928) as the collective term for the entire mass of dentine in the tooth plate.


The effect of destroying the whisker follicles in mice on the sensory nerve, the thalamocortical radiation and cortical barrel development. Electrolytic destruction of whisker follicles in mice on the day of birth has been found to cause degeneration in the sensory nerve fibres supplying the follicles. The severity of the degeneration has been assessed in animals between 2 and 20 days old by counting the total number of myelinated fibres in the maxillary nerves on both normal and lesioned sides. The degeneration is apparent after 2 days and by 20 days the nerve on the lesioned side contains only 38% of the normal fibre content. This degeneration has also been shown to involve the trigeminal root, central to the ganglion. In addition, the lesioning procedure modifies the terminations of thalamocortical fibres in the barrel region of the sensory cortex. These terminations are normally in clusters, each corresponding to a barrel, but, after lesioning the follicles, the terminals appear to be evenly distributed in layer IV and cortical barrel structures no longer develop. In postnatal mice, electrolytic destruction of whisker follicles had less effect upon maxillary nerve fibres and cortical barrels. The number of myelinated axons surviving until day 20 increased progressively with later lesioning to reach nearly 80% of the control level when lesions were made on day 10. Cortical barrels became secure earlier than the maxillary nerve, for a normal number of cortical barrels was present at day 12 when follicles were destroyed on day 4. The implications of these results for the formation of cortical barrels is discussed.


Developmental and ultrastructural observations on two stalked marine choanoflagellates, Acanthoecopsis spiculifera Norris and Acanthoeca spectabilis Ellis. Acanthoecopsis spiculifera and Acanthoeca spectabilis are stalked, loricate choanoflagellates found in littoral sea water pools. The two taxa are distinguished from each other by the arrangement of costae forming the lorica chamber. In addition, Acanthoecopsis spiculifera usually has a longer stalk and may be colonial, consisting of two or more attached individuals. Division in Acanthoeca results in the production of a juvenile, flagellated, protoplast without a lorica. After separation, the juvenile protoplast swims away, settles down and produces an accumulation of costal strips. When sufficient strips have been produced the lorica is rapidly assembled.


Radar-based studies of the migratory flight of grasshoppers in the middle Niger area of Mali. Some grasshopper species are pests of subsistence agriculture in the Sahelian zone of West Africa. Formulation of effective control strategies against these pests requires some knowledge of their migratory ability. In this paper a study is described in which radar was used to observe aspects of the nocturnal migratory behaviour of grasshoppers in the middle Niger delta. Mass take-off at dusk, layering and common orientation were regularly observed. Layering appeared to be related to air temperature. Mean orientation was often downwind but at other times crosswind headings occurred which added to the southerly component of the insects' displacement. Probable source areas of insects overflying the radar were identified by calculations of the insects' back-trajectories.


Trophoblast transferrin and transferrin receptors in the host--parasite relationship of human pregnancy. Transferrin and specific transferrin receptors are demonstrated on the microvillous surface of syncytiotrophoblast in human immature and term placentae by immuno histological techniques with the use of light and electron microscopy. That the distribution of transferrin is limited to the materno-foetal interface supports the hypothesis that binding of maternal transferrin to trophoblast receptors is involved in the process of iron transport to the foetus. Parallel studies with baboon placentae demonstrate the presence of trophoblast receptors which bind both baboon and human transferrin, thereby putting forward an experimental model which might be used to test the biological significance of placental transferrin receptors in primates. In addition, investigation of a large number of human cell lines shows that many transformed cells, but no normal cells (such as blood lymphocytes) or cells from primary culture (such as neonatal foreskin fibroblasts), possess the ability to bind transferrin to their membranes. These findings suggest that transferrin receptors may play important biological roles in addition to that of iron transport from mother to foetus. One such role could be the limitation of iron in intervillous spaces, thus depriving iron-requiring microorganisms of iron, hence serving as a non-specific factor of resistance for placentae. Another role for foetal transferrin receptors on trophoblasts could be to bind maternal transferrin at the materno-foetal interface, thus frustrating maternal immunosurveillance. This is similar to a mechahism used by schistosomes in the host-parasite relation where host proteins are bound by the parasite to escape immunological recognition. The presence of transferrin receptors on transformed cells suggests that this mechanism might also be employed by tumour cells. Finally, in view of previous studies which show that transferrin is required by stimulated lymphocytes to pass from the G1 to the S phase of cellular replication, it is proposed that trophoblast transferrin receptors could limit the amount of transferrin in intervillous spaces and thus impede the proliferation and possible cytotoxicity of maternal activated lymphocytes at the materno-foetal interface.


Intracellular potassium ion activity in resting and stimulated mouse pancreas and submandibular gland. Intracellular potassium ion activities (aiK+) and membrane potentials were measured with double-barrelled, potassium-specific microelectrodes in superfused mouse pancreas and submandibular gland. Stimulation with the cholinergic agonist bethanechol caused a marked decrease in aiK+ in the submandibular gland, whereas no change in aiK+ could be detected in the pancreas. This indicates that bethanechol increases the permeability of the cell membranes to potassium ions in the submandibular gland but not in the pancreas. Pancreatic acinar cells hyperpolarized promptly when the extracellular potassium ion activity was restored after a prolonged period of potassium deprivation. In comparison, the recovery of aiK+ was a slow process. This finding gives support to the view that the hyperpolarization is due to electrogenic sodium pumping.


Further observations on Calliacantha Leadbeater Choanoflagellata), with special reference to C. simplex sp. nov. from many parts of the world. C. simplex is a new species with an unusually wide geographical range, occurring at sea temperatures as varied as 0 degrees C under ice at Pt Barrow or -1 degrees C in arctic Canada, to 22 degrees C on the equator at the Galapagos Islands. The morphology and range of variation are illustrated by means of light microscopy, transmission electron microscopy and scanning electron microscopy applied to dry whole mounts prepared in situ from freshly-gathered wild material. Among the diagnostic structural features, special interest attaches to the position of the anterior transverse costa which is located unusually far back in comparison with other members of the genus; it is also shown to be within and not outside the ring of four longitudinal costae building up the lorica chamber, although this feature can only be ascertained by scanning. The differences between this species and C. natans (type species of the genus) are shown to be greater and to involve more characters than could previously have been recognized, and some possible functional implications are discussed in a preliminary way.


A computational theory of human stereo vision. An algorithm is proposed for solving the stereoscopic matching problem. The algorithm consists of five steps: (1) Each image is filtered at different orientations with bar masks of four sizes that increase with eccentricity; the equivalent filters are one or two octaves wide. (2) Zero-crossings in the filtered images, which roughly correspond to edges, are localized. Positions of the ends of lines and edges are also found. (3) For each mask orientation and size, matching takes place between pairs of zero-crossings or terminationss of the same sign in the two images, for a range of disparities up to about the width of the mask's central region. (4) Wide masks can control vergence movements, thus causing small masks to come into correspondence. (5) When a correspondence is achieved, it is stored in a dynamic buffer, called the 2 1/2-D sketch. It is shown that this proposal provides a theoretical framework for most existing psychophysical and neurophysiological data about stereopsis. Several critical experimental predictions are also made, for instance about the size of Panum's area under various conditions. The results of such experiments would tell us whether, for example, cooperativity is necessary for the matching process.


Ultrastructure of graniferous tracheary elements in the haustorium of Exocarpus bidwillii, a root hemi-parasite of the Santalaceae. The xylem in the body of the haustorium of E. bidwillii has the shape of an inverted conical flask with the expanded portion being known as the vascular core. The tracheary elements of the vascular core are notable for the occurrence of numerous granules within their lumina and the presence of mostly imperforate walls. Elsewhere in the haustorium graniferous tracheary elements are absent and the cells are usually ordinary vessel elements. Thin sections for transmission electron microscopy, post-stained in potassium permanganate, show that the secondary wall thickenings of the graniferous tracheary elements consist of eccentric layers in which the microfibrils of each successive layer run alternately longitudinally and transversely. The granules of the tracheary elements average 2 micrometer in diameter and consist of a homogeneous matrix which shows a fine fibrillar structure on high resolution. The granules are naked and mostly remain as separate structures within the lumen of the cell, but occasionally they fuse into small groups or irregular masses. In some cells the granules become transformed into fibrillar material that disperses throughout the lumen. This dispersed material may accumulate in vessels of the interrupted zone proximal to the vascular core. Occasionally, the granules also change into compacted amorphous masses that adhere to the walls of the cell. Ultrastructural cytochemistry confirms that the granules are protein and not starch as was originally believed for the Santalaceae. The function of the vascular core and its graniferous tracheary elements is discussed and we suggest that it might help regulate the pressure and flow of xylem sap entering the parasite from the host. Graniferous tracheary elements in the Santalaceae and in root parasites of the Serophulariaceae are compared and it is concluded that they represent examples of convergent evolution.


Differentiated regions of human placental cell surface associated with attachment of chorionic villi, phagocytosis of maternal erythrocytes and syncytiotrophoblast repair. Scanning electron micrographs of human placental cell surface show: (1) Differentiated zones of trophoblast which may be covered by fewer 'microvilli' than the adjacent syncytial cell surface and which extend as a narrow, usually distal protrusion of the chorionic villus. This narrow outgrowth terminates as a fractured end. Presumably since preparations were obtained from therapeutic terminations of pregnancy or Caesarian deliveries these broken ends represent the yield point in the anchoring 'villi' ruptured as a result of surgery. Similar anchoring 'villi' with fractured ends were observed in unfixed material with the use of Nomarski interference contrast microscopy. (2) It appears that, during apparent phagocytic uptake of maternal erythrocytes by syncytiotrophoblast, cell surface lining the forming vacuole still retains an irregular microvillous surface. This observation indicates the potential location of phagocytosis receptors for red blood cells in the placental cell surface. (3) Areas of human placenta which appears to have been damaged and may be undergoing repair exhibit masses of cells with conspicuous microvillar cell surfaces. The origin of these cells is discussed in relation to the usual processes of syncytiotrophoblast formation.


Stress distribution in the scapula studied by neutron diffraction. High intensity neutron beams provide a method of measuring the preferred orientation of apatite crystals in bulk samples of bone. Measurements at seven different sites on the scapula show that the c axes of the crystals lie preferentially along the directions of pull of the attached muscles. The highest orientation is found at positions under the influence of only a single group of muscles, such as M. teres major or M. infraspinatus. In intermediate regions a multiple distribution of crystals is found, able to withstand stresses in more than one direction. The technique provides a method of assessing the distribution of stress in bones.


The ganglion cell layer of the retina of the rat: a Golgi study. In whole-mounts of Golgi stained rat retinae four cell types are described in the ganglion cell layer. Three of these cell types are considered to be analogous to the alpha, delta and gamma cells described in the cat retina by Boycott & Wässle (1974). The fourth cell type is thoughtt to be a displaced amacrine cell. All the cell types described are present in all parts of the retina. There is no evidence for an increase in dendritic field size with increasing distance from the optic disk.


An easily assembled and inexpensive apparatus for continuous monitoring of expired carbon dioxide concentrations in artificially ventilated animals. An inexpensive and simple apparatus for monitoring expired carbon dioxide concentrations in artificially ventilated animal preparations is described. The system may be rapidly and easily constructed using a standard recording pH electrometer and a commercially available Pco2 electrode. This assembly has been proven to be an effective and sensitive means of monitoring CO2 levels, detecting changes in this gas within one-half percentage.


Adrenergic activity of ortho-, meta-, and para-octopamine. DL-o-, and p-octopamine were tested for beta- and alpha-adrenergic activity in rats. When compared to DL-isoproterenol, a beta-adrenergic agonist, all three isomers failed to show significant beta-adrenergic activity as assessed by intiation of thirst and by increase in tail skin temperature. All three isomers increased mean blood pressure in pentolinium-blocked rats. Of the three isomers, m-octopamine possessed the greatest alpha-adrenergic activity. When the responses were compared with those induced by L-norepinephrine, the order of activities was: 1:0.01 :0.0005 :0.0007 for norepinephrine, m-, p- and o-octopamine, respectively. Thus, DL-m-octopamine has about 1/100th the alpha-adrenergic activity of L-norepinephrine.


Distribution of glutamate dehydrogenase and glutamine synthetase activity in the sheep and chicken digestive tract. Glutamate dehydrogenase (GLDH, EC 1.4.1.3) and glutamine synthetase (GS, EC 6.3.1.2) activity were determined in the contents and tissues of the various parts of the sheep and chicken digestive tract, GLDH activity in the tissues of the sheep omasum, duodenum, rumen, reticulum, colon, caecum, jejunum and ileum ranged from 3.25+/-0.7 U (mumol/g dry weight . min) to 5.94+/-2.28 U; in the abomasum it was 9.67+/-1.27 U. GLDH activity in the contents of the ileum, abomasum, jejunum and duodenum varied from 0.85+/-0.19 U to 3.29+/-0.53 U and in the colon, caecum, reticulum, omasum and rumen from 6.34+/-2.64 U to 16.96+/-3.83 U. GS activity in the tissues of these parts of the digestive tract varied from 2.8+/-0.59 U to 8.6+/-1.4 U and their contents from 2.49+/-0.85 U to 10.76+/-2 U. GS activity in the contents of the colon was very low (0.26+/-0.07 U). In the tissues of the chicken duodenum, caecum, jejunum and ileum we found GLDH activity of 4.68+/-1.64 U to 7.96+/-1.73 U; in their contents it was 3.31+/-1.06 U to 3.8+/-0.73, but in the caecum it attained up to 66.7+/-24.3 U. GS activity was high from 57.6+/-2.0 U to 231+/-84 U in the tissues and 357+/-53 U to 383+/-76 U in the contents (in the caecum up to 2,500+/-233 U). The results show that conditions for the utilization of ammonia are present in the tissues and the contents in the whole of the sheep and chicken digestive apparatus. The hypothesis is confirmed that the different ability of ruminants and fowls to utilize ammonia formed from urea added to their feed, including ammonia formed by hydrolysis of blood urea, is due to the different GLDH and GS activity in their digestive tract as well as in their liver.


Development of spontaneous motility in chick embryos. The effect of drugs influencing central aminergic systems. The development of changes in spontaneous motor activity after the systemic administration of substances interfering with the function of central aminergic systems was studied in 11- to 19-day chick embryos. Reserpine was administered in a dose of 2.5 mg/kg egg weight, chlorpromazine in a dose of 3 mg/kg e.w. and dehydrobenzperidol in a dose of 6 mg/kg e.w. to the embryonal membranes. The effect of reserpine was studied for 4 hours and the effect of chlorpromazine and dehydrobenzperidol for 60 min after administration. None of the above substances produced significant changes in the frequency of spontaneous movements up to the 13th day of incubation. From the 15th day they began to depress spontaneous motility, the intensity and duration of which increased with the embryos' age. Reserpine had the strongest effect. The results are interpreted with reference to development of the participation of central aminergic systems in supraspinal control of spontaneous motility in chick embryos in the second half of embryogenesis. They are further evidence of the integration of aminergic systems after the 15th day of incubation.


[Sociopsychiatric treatment combination in patients who are partly inpatients and genuine outpatients: definition and comparison (author's transl)]. The article gives a definition and brief description of those possibilities of treatment which are important in the sociopsychiatric therapy of psychoses: sociotherapy, therapy with neuroleptics, and psychotherapy as such, as well as their various combinations. Basing on a representative random trial from the fields of outpatient and nightpatient wards, the distribution of therapeutic potential among these combinations is described and outlined in a manner customary for the work bone by the Zürich Sociopsychiatric Service. It is evident, despite the fact that the work performed at our hospital is basically of the psychotherapeutic nature, patients can be rehabilitated with a lower level of neuroleptics provided sufficient sociotherapeutic measures are offered, including satisfactory psychotherapeutic efforts--the chances of meeting these demands being greater in our night ward. Patients who cannot be fully rehabilitated but more or less integrated, did not show such obvious differences, whereas the more intense sociotherapeutic programme of the nigth ward enabled the reintegration even of the nigth ward enabled the reintegration even of more seriously disturbed patients than could be achieved by mere outpatient follow-up treatment.


The Geller-Seifter conflict paradigm with incremental shock. The typical Geller-Seifter conflict paradigm for predicting clinical efficacy of anxiolytics is a mult VI/CRF schedule in which response rates in the CRF (conflict) portion are depressed by response-contingent electric shock. In 1-h sessions, anxiolytics raise the depressed conflict rates. Recently it was shown that replacing the single shock level with an arrangement whereby shock begins at zero and is increased with each response in the conflict portion produced more orderly data and facilitated training and maintenance of experimental subjects; chlordiazepoxide was the test drug. In the present study, those results are replicated in 30-min sessions, and the incremental paradigm is demonstrated to be as specific for anxiolytics as the standard Geller-Seifter paradigm. The possibility of very short sessions is suggested.


Bedtime flurazepam and the human circadian rhythm of spontaneous motility. Sixteen male students received bedtime placebo and flurazepam 30 mg at home in a counter-balanced double-blind, crossover design. For 24 h after each treatment the subjects' spontaneous motor activity was recorded each 15 min with an unobtrusive actometer, worn as the subjects attended classes. The circadian activity curves were submitted to cosinor analyses. The 24 h post-flurazepam activity was a mean of 15.1% lower than post-placebo activity (P less than 0.025). On the average, both the nocturnal through and the daytime peak of motility dropped; the latter change was greater, reducing by a mean of 19.4% the amplitude of the circadian rhythm of activity (P greater than 0.01). the timing, or phase, of the rhythm was not shifted. Although the drug did not consistently modify reports of subjective feelings on the Profile of Mood States (POMS), 13 subjects correctly discriminated drug from placebo sessions (P less than 0.05). A bedtime dose of 30 mg of flurazepam appears to significantly reduce spontaneous human motility that night and during the next day. Activity recording revealed an important residual, behavioral effect of the drug which was not reflected in POMS reports of subjective feelings, suggesting that activity recording may provide a more sensitive measure for psychotropic drug effects.


A pharmacologic study of analgesia produced by stimulation of the nucleus locus coeruleus. Pharmacologic studies of analgesia produced by stimulation of the nucleus locus coeruleus (LC) were conducted using the rat hot-plate test. A correlation between self-stimulation and analgesia produced by stimulation of LC was found. Analgesia produced by LC stimulation was attenuated by naloxone, a morphine antagonist, cyproheptidine, a serotonin antagonist, and WB-4101, an alpha-adrenergic antagonist. The analgesia was absent in 6-OHDA-treated rats. Catecholamine synthesis inhibition by a combination of reserpine and AMT or more specific inhibition of noradrenaline synthesis by DDC elevated latency to paw lick and yet did not affect stimulation-produced analgesia. It is suggested that morphinergic, serotonergic, and alpha-adrenergic mechanisms mediate LC stimulation produced analgesia.


GABAergic and glycinergic mechanisms within the substantia nigra: pharmacological specificity of dopamine-independent contralateral turning behavior and interactions with other neurotransmitters. The pharmacological specificity of the GABA agonist muscimol-induced contralateral turning behavior after unilateral injection into substantia nigra pars reticulata (SNR) has been studied. Muscimol-induced turning was antagonized by intranigral bicuculline methochloride (BMC) and picrotoxin, whereas antagonists of glycine, morphine, dopamine, noradrenaline, and serotonin were ineffective. Glycine induced a qualitatively similar turning behavior which was strychnine-sensitive but relatively BMC and picrotoxin-insensitive. Other drugs, including substance P, kainic acid, clonidine, oxymetazoline, serotonin, and carbachol, induced turning that could be dissociated from the effect of muscimol. Muscimol-induced turning was dopamine-independent, indicated by resistance to haloperidol (1 mg/kg), to pretreatment with reserpine (7.5 mg/kg) plus alpha-methyl-p-tyrosine (200 mg/kg), to haloperidol injections into the SNR, striatum and nucleus accumbens, and finally to kainic acid lesions of the striatum. 6-Hydroxydopamine lesions increased the efficacy of intranigral muscimol, while kainic acid lesions of the SNR antagonized muscimol. Muscimol-induced turning was inhibited by oxotremorine (0.25 mg/kg), by intranigral carbachol, and by apomorphine (0.1--0.5 mg/kg), but only moderately by intranigrally injected apomorphine. These data suggest specificity of GABA-agonist-induced contralateral turning and indicate an interaction between nigral GABA and other neurotransmitters, particularly dopamine and acetylcholine.


[The gamma-glutamyl transpeptidase (GGTP) as an index for the diagnosis of chronic alcoholic cholestatic hepatitis (author's transl)]. The GGTP is an enzyme localized, in the liver cell, inside microsome. At beginning the use of the GGTP was introduced for the diagnosis of chronic hepatitis; after it was noted as this was steady increased in the cholestasis and in the alcoholism. We have, hence, wanted to experiment if the changing of the level of the GGTP allowed to us a diagnosis of chronic alcoholic hepatitis. Our research is based on seventy-five patients with several liver diseases. It has been noted as the highest levels of the GGTP have appeared in cases of chronic alcoholic hepatitis with signs, histologicals and biochemicals, o cholestasis. In fact we have, on overage, levels of 955 mU/ml in the chronic alcoholic hepatitis with signs of cholestasis and of 135 mU/ml in that without it. In conclusion the GGTP is a good index for the diagnosis of chronic alcoholic cholestatic hepatitis.


[The determination of phosphohexose isomerase in patients with cancer of breast and uterus. A comparison with other tests (author's transl)]. The levels of PHI are evaluated in 94 patients, who are classified by histological, scintigraphycal, radiological, biochemical and clinical test in: 16 patients, who suffer from some premalignant lesions of breast and uterus, 15 patients, who suffer from cancer of breast without metastases, 20 patients who suffer from cancer of breast with metastases, 18 patients who suffer from with cancer of uterus without metastases, 25 patients who suffer from cancer of uterus with metastases. The PHI activity is also evaluated in relation to the activity of other enzymes (LDH, AIP, G-GT). It has been revealed that: a) the PHI activity keeps within limits of normal value in patients who suffer from some pre-malignant lesions; b) all the patients suffer from cancer of breast without metastases show normal levels of PHI; c) in the patients with cancer of breast with metastases: 5 patients show normal levels of PHI, 5 patients show levels of PHI within limits, certainly 10 patients show pathological levels; d) in patients with cancer of uterus without metastases the value of enzymes results pathological in 6 patients, 6 patients show levels of PHI within limits that are above average and 6 patients show normal levels of PHI; e) the value of PHI always results high in patients with cancer of uterus with metastases.


Evaluation of pH monitoring as a method of processor control. Sensitometry and pH values of the developer solution were compared in controlled over-replenishment, developer depletion, fixer contamination experiments, and on a daily quality control basis. The purpose of these comparisons was to evaluate the potential of pH monitoring as a method of processor control, or a supplement to sensitometry as a method of quality control. Reasonable correlation was found between pH values and film density in two of the three experiments but little or no correlation was found in the third experiment and on a day-to-day basis. The conclusion drawn from these comparisons is that pH monitoring has several limitations which render it unsuitable as a method of daily processor quality control as either a primary or supplementary technique. Sensitometry takes into account all the variables encountered in film processing and is the clear method of choice for processor quality control.


[Comparative study of chicken liver xanthine dehydrogenase and bovine liver xanthine oxidase. dehydrogenase activity of xanthine oxidase (author's transl)]. A method to purify bovine liver xanthine oxidase in described, with which samples of 256-fold specific activity with respect to the initial homogenate are obtained. Bovine liver xanthine oxidase and chicken liver xanthine dehydrogenase with oxygen as electron acceptor exhibit similar profile in pKM and log V versus pH plots. With NAD+ as electron acceptor a different profile in the pKM xanthine plot is obtained for chicken liver xanthine dehydrogenase. However three inflection points at the same pH values appear in all plots. Both enzymes are irreversibly inhibited by pCMB and reversibly by N-ethylmaleimide and by iodoacetamide, with competitive and uncompetitive type inhibitions respectively. These results suggest that NAD+ alters the enzymatic action since its binding to the enzyme antecedes the binding of xanthine to the xanthine oxidase molecule, without undergoing itself any modification. 0.15 M DDT of DTE treatment of bovine liver xanthine oxidase gives to the enzyme a permanent activity with NAD+ without modifying its activity with oxygen. The enzyme thus treated produces parallel straight lines in Lineweaver-Burk plots.


[Influence of alpha and beta blocking agents on recovery of intestinal transit and postoperative complications in aged patients]. Following the recovery of intestinal peristaltic movements in medium and advanced age patients in whom major surgery had been performed, after an adequate preparation with and blocking agents, as compared with the control group, a shortening was noted, of the intestinal paresis period in both age groups. The early recovery of intestinal transit had positive effects on the postoperative evolution of the patients, especially in the aged ones, and allowed for an early resumption of oral alimentation, reducing abdominal meteorization, as well as the number and the severity of local and general complications.


DDT-induced myoclonus: serotonin and alpha noradrenergic interaction. p,p'-DDT (600 mg/kg) produces myoclonic activity in mice which can be reduced by L-5-hydroxytryptophan (L-5HTP) (200 mg/kg), H75/12 (25 mg/kg), serotonin uptake blockers and two alpha-receptor blockers, phenoxybenzamine (5 mg/kg) and trazodone (5 mg/kg). Decreasing endogenous brain serotonin by pretreatment with p-chlorophenylalanine (400 mg/kg i.p.) blocked the antimyoclonic action of all of these drugs except L-5HTP. Seven other alpha-receptor blockers (phentolamine, tolazoline, yohimbine, azapetine, aceperone, nicergoline and prazosin) potentiated the antimyoclonic activity of a small dose of L-5HTP (50 mg/kg) in this animal model. We postulate that an alpha noradrenergic inhibitory synapse may be located in the neural circuit connecting a serotonergic neuron to the final motor response (p,p'-DDT-induced myoclonus).


An in vitro rat liver microsomal system for conjugating fatty acids to 11-hydroxy-delta 9-tetrahydrocannabinol. We have previously identified long-retained metabolites of delta 9-tetrahydrocannabinol (delta 9-THC) and delta 8-tetrahydrocannabinol (delta 8-THC) in the rat as fatty acid conjugates of 11-hydroxy-delta 9-THC and 11-hydroxy-delta 8-THC. These metabolites can be produced in vitro using a rat liver microsomal energy-dependent esterase system.


Influence of respiratory acidosis and alkalosis on volume of distribution of theophylline in dogs. The volume of distribution of theophylline at nomal pH, and following induction of respiratory acidosis and alkalosis, was studied in four dogs in a three-way crossover design. Although serum half-lives of theophylline varied widely, and acidemia prolonged the time required for distribution equilibration, the volumes of distribution were almost identical for each of the three experimental conditions assuming one compartment pharmacokinetics apply.


Morphine lethality in rats: effects of various central receptor blocking agents. A previous report of a lethal potentiation between sublethal doses of morphine and the beta-adrenergic blocker propranolol was confirmed for Sprague-Dawley rats. An alpha-adrenergic blocker, phentolamine, also showed a lesser but significant potentiation, as did a moderate dose of atropine. No synergism was noted between morphine and methylatropine, haloperidol or methysergide. Phentolamine and a lower dose of atropine, which did not synergize with morphine, both added significantly to the lethality of the combination of morphine and propranolol, whereas methylatropine, haloperidol and methysergide had no significant effect to synergize or antagonize mortality.


Biochemical evidence of cocarcinogenesis: tumor promoting agent enhances methylnitrosourea activation of rat guanylate cyclase activity. The two-stage or cocarcinogenic  hypothesis of carcinogenesis involves an initiator (carcinogen) and a promotor (cocarcinogen) being utilized in combination to produce more tumors than either would alone. This theory was tested at the cellular level utilizing Tumor Promoting Agent, 12-0-tetradecanoly-phorbol-13-acetate, (promotor) in combination with submaximal and maximal doses of methylnitrosourea (initiator). Tumor promoting agent, which can cause some tumors itself, was found to enhance the activity of guanylate cyclase (E.C.4.6.1.2.), an enzyme that has been associated with normal and abnormal growth. Tumor promoting agent when utilized in combination with submaximal stimulatory doses of methylnitrosourea had an additive effect on guanylate cyclase activity, but the agent had no further additive effect on guanylate cyclase activation when methylnitrosourea was utilized in maximal stimulatory doses. These results indicate a carcinogen acting alone without a promoter can maximally activate guanylate cyclase and would suggest that at the cellular level a promotor is not absolutely necessary for the changes observed morphologically in canerous cells. The promotor, however, did enhance the enzyme's activity when a submaximal dose of the carcinogen was used indicating that promoting agents, at least biochemically, appear capable of potentially contributing to the development of a cancerous cell.


Upper respiratory tract spread of group B streptococci type I b in a kindergarten. In a kindergarten with 42 children and 17 female staff members, an epidemic of group B streptococcal carriage in the upper respiratory tract occurred. In the middle of February 1978, 6 children and 5 adults carried type I b streptococci in the throat while only 2 of these 11 were carriers 2 weeks later. Only one other streptococcus, belonging to type II, was found in the throat specimens. Five strains other than type I b were found in the urogenital tract of the staff. Three type I b throat carriers were also urogenital carriers of this type. The spread of type I b streptococci could have resulted from co-spreading with other upper respiratory tract pathogens found, including group A streptococci of type 12. Haemophilus influenzae, Branhamella catarrhalis and pneumococci. Estimation of antibodies with radiolabelled protein A indicated an immune response to type I b, but not to types I a, II or III group B streptococci in the staff compared with healthy blood donors.


Antibiotic susceptibility of anaerobic bacteria with special reference to Bacteroides fragilis. It was shown that recent Swedish clinical isolates of anaerobic bacteria are susceptible to many antibiotics by the agar dilution method with the exception of the Bacteroides group versus beta-lactam antibiotics or tetracyclines. Strains of B. fragilis were inhibited by 4--greater than 128 micrograms benzylpenicillin or cephalothin/ml, 1.0--64 micrograms cefoxitin/ml, 0.064--2 micrograms clindamycin or metronidazole/ml, 2--8 micrograms chloramphenicol/ml, 2--16 micrograms fusidic acid/ml and 0.032--32 micrograms doxycycline/ml. Resistance to beta-lactam antibiotics was partly due to the production of beta-lactamase. Growth of beta-lactamase producing strains in the presence of enzyme inhibitors such as clavulanic acid or CP-45899 together with cephaloridine lowered the MIC's manyfold. Cefoxitin with relative resistance to beta-lactamases inhibited the majority of the strains at 8 micrograms/ml. Cefoxitin-resistant strains (MIC greater than or equal to 16 micrograms/ml) were also resistant to the new cephalosporins BL-S786 and HR-756 as well as to the new cefamycins A, B, CL619-183, CS-1170 and Sq-14359 and to thienamycin. Cefamycin CL619-183, only showed a slightly higher in vitro activity than cefoxitin. Resistance to the cefamycins could not be correlated to the production of beta-lactamases.


Anaerobic pulmonary infections.

Anaerobic pulmonary infections. The main cause of anaerobic pulmonary infections is aspiration of saliva, upper airway secretions or gastric content. Predisposing conditions include prominent dental disease, chronic upper respiratory tract infections and reduced consciousness. Fusobacterium nucleatum, Bacteroides melaninogenicus and anaerobic Gram-positive cocci are the most frequently encountered organisms. The clinical presentations are lung abscess, lung gangrene and empyema, which all tend to take a slow and indolent course. Preferred localization are dependent lung segments, most often on the right side. For bacteriological examination in these infections, only transtracheal aspirate and aspirate from the lung or pleural space are considered adequate. In 26 cases of empyema treated in our hospital during the last 3 years, adequate specimens had been taken in 19. Fifteen had been adequately examined, and anaerobes were cultured in 6. Among 29 abscesses treated during the same period, adequate specimens had been taken in only 14, and 11 had been properly examined. Seven specimens grew anaerobes on culture. In prospective studies of transtracheal aspirate in 15 chronic bronchitics without emphysema, anaerobes were not demonstrated. In 11 patients with bronchiectasis, anaerobic bacteria were cultured in 3. Finally, no anaerobic bacteria could be demonstrated in the transtracheal aspirate from 76 patients with acute exacerbation of chronic bronchitis. Anaerobic, pulmonary infections do not represent an intriguing medical problem in our region. However, knowledge of these infections is necessary to secure adequacy in collection of specimens and in their bacteriological examination.


Endorphins, dopamine, and schizophrenia. The theory that alterations of dopaminergic synaptic transmission may play a role in the pathogenesis of schizophrenia is widely accepted. A more recent theory links the endorphin system to the etiology of schizophrenia. We propose that these two theories may be combined into a single model. Recent neurochemical and pharmacological findings have indicated close functional relationships between the endorphin and dopamine systems. Endorphins modulate dopaminergic synaptic transmission by exerting both presynaptic and postsynaptic effects. On the molecular level, this modulation may involve the activity of nucleotide cyclases and protein phosphorylation systems. Thus, the dopaminergic neuronal hyperactivity, currently believed to be related to schizophrenia, may be caused by a primary alteration in the endorphin system. Several hypotheses about the nature of that alteration have been advanced and tested in therapeutic experiments with schizophrenic patients. These experiments have not yet yielded definitive results.


Research in endorphins and schizophrenia. It has been suggested that the newly discovered endogenous opiate peptides (called endorphins) might play a role in the symptoms of schizophrenia. The administration of narcotic antagonists provides both a test of the hypothesis and a potential treatment. In this article, we review the methods by which data have been gathered to test endorphin involvement in schizophrenia. Alternative strategies, which hold greater promise of producing conclusive positive or negative evidence, include exploitation of individual differences, use of psychophysiological measures, genetic strategies, and multivariate statistical techniques with larger sample sizes.


In search of treatment for tardive dyskinesia: review of the literature. Studies on the treatments for neuroleptic-induced tardive dyskinesia published in the English literature until August 1978 are reviewed. There is a yet no single satisfactory method of treatment for tardive dyskinesia. Withdrawal of neuroleptics results in a remission of symptoms in younger and non-brain-damaged patients. Paradoxically, the most effective treatment for suppressing dyskinesia is administration of neuroleptics. The possibility that continued use of neuroleptics in dyskinesia patients produces irreversible brain damage remains to be validated (or invalidated). Anticholinergic and dopaminergic drugs are of no value in the treatment of tardive dyskinesia. Cholinergic drugs have not lived up to their initial promising results in this condition. About one third of the dyskinetic subjects seem to respond to various nonspecific measures. Tardive dyskinesia probably consists of at least two subtypes-- reversible and persistent. Methodological aspects of earlier studies and possibilities for future research in this field are discussed. Suggestions for treatment of individual cases are also outlined.


A non-neuroleptic treatment for schizophrenia: analysis of the two-year postdischarge risk of relapse. The efficacy of antipsychotic drug maintenance in reducing the risk of relapse among previously hospitalized schizophrenic patients has been well documented. However, data from an ongoing study comparing two cohorts of young first admission schizophrenics--one receiving neuroleptic-oriented treatment on the wards of a community mental health center (CMHC), the other an intensive interpersonal approach in a small homelike facility in the community (Soteria House)--raise questions about the routine use of neuroleptics with this population. Our questioning of this practice is based on data analyzed from these two cohorts by means of the life table, a statistical technique appropriate for longitudinal studies. Data are presented in two ways: (1) The overall effectiveness of the two independent treatment programs (Soteria, N = 32, vs. CMHC, N = 36) is compared in terms of the probabilities of not being readmitted over the 2-year postdischarge interval. (2) Analyses that look at the influence of the original treatment setting and postdischarge antipsychotic drug status on readmission rates are presented. Program comparisons reveal Soteria patients to have a consistently higher survival rate than CMHC patients throughout 2 years postdischarge. At 12 months postdischarge, the cumulative probability of remaining well (no readmissions) significantly favors the Soteria patients (p less than .05, Mantel chi2). The overall results of the Soteria program were achieved despite the fact that all CMHC patients received neuroleptics during their original inpatient stays and about 50 percent were maintained on neuroleptics up to the point of readmission or study termination, whereas only 10 percent of Soteria subjects were treated with or maintained on neuroleptics. The survival rates by postdischarge drug status and program affiliation show the Soteria no-drug group to have the highest proportion of survivors at almost every interval throughout 24 months, the CMHC drug-maintained group to have the lowest survival rate, and the CMHC unmaintained group to be surviving at a rate generally comparable to the Soteria no-drug group.


[Liver cirrhosis. Clinical and biological aspects]. The symptoms of cirrhosis are inconsistent and appear late in the course of the disease. Laboratory tests are also of variable value; generally speaking, cytolysis is observed infrequently. The gamma-GT test is the most sensitive in alcoholic cirrhosis, but may be more an expression of the degree of alcoholism than of the hepatic lesion per se. In cirrhosis, the best diagnostic method is a combination of laparoscopy and puncture biopsy. Endoscopy permits diagnosis not only of the hepatic lesion but also of the complications which may ensure, such as portal hypertension and ascites. Alcoholic abstinence appears to improve the prognosis of alcoholic cirrhosis. The prognosis in this condition may, in fact, be better than has been suspected.


Inosine may be an endogenous ligand for benzodiazepine receptors on cultured spinal neurons. Mouse spinal neurons grown in tissue culture were used to study the membrane effects of the benzodiazepine flurazepam and the naturally occurring purine nucleoside inosine, which competes for benzodiazepine receptor sites in the central nervous system. Application of inosine elicited two types of transmitter-like membrane effects: a rapidly desensitizing excitatory response and a nondesensitizing inhibitory response. Flurazepam produced a similar excitatory response which showed cross-desensitization with the purine excitation. Flurazepam also blocked the inhibitory inosine response. The results provide electrophysiological evidence that an endogenous purine can activate two different conductances on spinal neurons and that flurazepam can activate one of the conductances and antagonize the other.


Effect of purified beta glucuronidase infusion in normal dogs and dogs with acidosis. The effects of systemic infusion of purified beta glucuronidase, lactic acid and a combination of these were studied in normal dogs from the viewpoints of hemodynamics and blood coagulation. In none of the groups was an obvious deterioration in arterial blood pressure, pulse rate, central venous pressure, portal venous pressure and electrocardiogram observed after the infusions. On the other hand, beta glucuronidase infusion with preceding acidosis caused substantial thrombocytopenia accompanied by a decrease in fibrinogen levels and abnormal thromboelastogram. A similar trend was found by the infusion of beta glucuronidase only. An intermediate abnormality was found by the infusion of lactic acid alone. Histologically, fibrin clots in the pulmonary arteries were often observed in the dogs of all groups, but the quantitative difference among the groups was difficult to evaluate. In the present investigation, shock could not be produced, but other data seemed to indicate that increased levels of acid hydrolases in the blood are concerned with deterioration and irreversibility of shock, especially in an acidotic condition.


Cerebral anoxia: effect of deep hypothermia and pH. Deep hypothermic circulatory arrest facilitates repair of congenital cardiac anomalies in infants. It is known empirically that hypothermia protects against central nervous system (CNS) ischemic damage. The Q10O2 is only 2.2 for brain and thus a decrease in metabolic rate does not fully account for protective effects of hypothermia. Since enthalpy of dissociation of H2O is high (approximately 7 kcal/mole), its pH is temperature dependent (7.0 at 25 degrees C, 7.4 at 20 degrees C) and hypothermia may in part protect by its influence on hydrogen ion concentration. A manifestation of CNS susceptibility to ischemia is an obstruction of the microcirculation [no-reflow lesion (NRL)] demonstrated by infusion of carbon black into the cerebral circulation after a period of circulatory arrest. White lesions (NRL) against a gray background on cut section of brain increase in size with increasing time of arrest. The effect of anoxia versus circulatory arrest, brain temperature, and extracellular brain pH on NRL was studied in 45 mongrel dogs, subjected to varying periods of N2-induced anoxia on cardiopulmonary bypass (CPB) at 37 degrees C or 20 degrees C. In some studies jugular venous pH was adjusted by infusion of NaHCO3 or HCl. Control groups included normothermic CPB without anoxic and normothermic CPB, anoxia, and equimolar NaCl infusion. NRL was quantified by planimetry of photographs of cut sections of brain. These results confirm that NRL is abated by hypothermia and suggest that (1) NRL is a function of anoxia and not arrested circulation since perfusion with N2 at 37 degrees C does not protect the brain (i.e., NRL is not solely related to "critical reopening pressure") and (2) NRL is in part a function of extracellular pH.


The beta-adrenergic blocking agents and the treatment of glaucoma. The autonomic nervous system is divided into the parasympathetic and sympathetic systems, with three types of adrenergic receptors: alpha (smooth muscle contraction), beta1 (cardiac acceleration and fatty acid mobilization) and beta2 (smooth muscle relaxation). Substances affecting the function of the adrenergic system are the agonists or stimulators, which mimic the effects of endogenous norepinephrine or epinephrine, and antagonists or blockers, which block the receptors and prevent stimulation by the agonists. Autonomic stimulation in the eye mediates various changes which apparently affect outflow facility and rate of formation of aqueous humor. Alteration of either or both of these factors by autonomic agonists or antagonists may have a direct or an indirect effect on intraocular pressure. Beta-adrenergic blocking substances have been used to treat a variety of diseases. Some of the effects of these drugs are attributable to properties other than beta blockade, such as intrinsic sympathomimetic activity and local anaesthetic activity. Side effects of this class of drugs require caution in cases of congestive heart failure and in asthmatics. Autonomic agents used in the treatment of ocular hypertension and glaucoma include pilocarpine, a chilinergic agonist, epinephrine, an adrenergic agonist, and various beta adrenergic blockers or antagonists including propranolol, atenolol and timolol. The physico-chemical properties and pharmacokinetics of timolol are reviewed. Data showing a significant reduction in intraocular pressure as a result of ocular instillation of timolol are presented. Reduction of the rate of aqueous formation appears to be the mechanism of action. A low incidence of non-serious side effects is reported.


Spontaneous platelet aggregation in cerebrovascular disease II. Further characterisation of the platelet defect. A group of 186 patients with Transient Ischaemic Attacks (TIA) or cerebral infarction (CI) was found to demonstrate in vitro Spontaneous Platelet Aggregation (SPA) in 39% of those studied. Of the 176 normal subjects studied the incidence on in vitro SPA was found to be 5%. Further investigation of the phenomenon of SPA revealed that: 1. it is associated with ADP-hyperaggregability, i. e. the threshold concentration to induce second wave aggregation is decreased; 2. it is dependant on the increase in pH which occurs in platelet-rich plasma stirring in an aggregometer while concurrent ADP-hyperaggregability is independant of this change in pH; 3. it is associated with malondialdehyde production and the release of endogenous 5-hydroxytryptamine; and that 4. in addition Km and Vmax values for [14c]-5HT incorporation are normal; and that 5. no gross abnormalities of the platelet membrane glycoproteins were apparent although occasionally glycoprotein III was found to be increased. This study demonstrates abnormal platelet behaviour in patients with TIA and CI where the enzyme system involved in thromboxane production is sufficiently stimulated, by stirring alone, to induce aggregation of platelets and the release reaction. Acetylsalicylic acid abolishes SPA and prolongs the bleeding time with similar characteristics as has been described for normal individuals. Plasma beta-thromboglobulin levels are significantly increased in the patients studied. However, no correlation was established with the incidence of in vitro SPA.


Studies on the adrenergic systems of the eye at the Wilmer Institute. The study of the ocular adrenergic systems at the Wilmer Institute over the last 40 years began with the examination of the formation and outflow of aqueous humor by Jonas Friedenwald and his co-workers in the early 1940's. At that time, researchers were attempting to understand the mechanisms of fluid dynamics in the eye, with the idea of altering these mechanisms to alleviate glaucoma only a distant goal. In the late 1950's, Langham and others reported on the effect of superior cervical ganglionectomy on intraocular pressure, following this work with a succession of papers on the relationship between alpha and beta adrenergic substances and aqueous humor dynamics. Sears, in collaboration with Bárány, described the effects of alpha and beta adrenergic substances on outflow resistance. Eakins, in 1963, suggested a mechanism of action for isoproterenol in the lowering of intraocular pressure. Work on timolol at Wilmer began with a report from Radius, Diamond, Pollack and Langham covering experimental studies with rabbits and clinical studies of the drug's ocular hypotensive effects on glaucoma patients. Richter and others also studied a small number of patients on maximal therapy and found further intraocular pressure reduction with added timolol.


Characterization of two new enzymatic activities of the rat ventral prostate: 5 alpha-androstane-3 beta, 17 beta-diol 6 alpha-hydroxylase and 5 alpha-androstane-3 beta, 17 beta-diol 7 alpha-hydroxylase. This study has characterized two new enzymatic hydroxylase activities specific for 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol) in the rat ventral prostate: 5 alpha-androstane-3 beta, 17 beta-diol 6 alpha-hydroxylase (6 alpha-hydroxylase) and 5 alpha-androstane-3 beta, 17 beta-diol 7 alpha-hydroxylase (7 alpha-hydroxylase). Both of these irreversible hydroxylase activities require NADPH and are localized in the microsomal fraction of the prostate. The apparent Km for 3 beta-diol is 2.5 microM for both the 6 alpha- and 7 alpha-hydroxylase activities. The apparent Km for NADPH is 7.6 microM for the 6 alpha-hydroxylase and 7.0 microM for the 7 alpha-hydroxylase. The pH optimum for both activities is 7.4. Several steroid inhibitors of these hydroxylase activities in vitro were identified including cholesterol, progesterone, and estradiol. Estradiol was found in vitro to be a noncompetitive inhibitor (Ki = 5 microM). Injection of estradiol into intact male rats, simultaneously receiving exogenous testosterone, also produced a significant lowering of the 6 alpha-plus 7 alpha-hydroxylase activities. Both the 6 alpha- and 7 alpha-hydroxylase were found to be androgen sensitive. Following castration there is a rapid decrease in both activities.


Suppression of graft-versus-host reactions in rats bearing implants in the anterior chamber of the eye. The graft-versus-host (GVH) response of spleen cells from rats bearing either orthotopic skin grafts or allogeneic implants in the anterior chamber of the eye was evaluated using popliteal lymph node (PLN) assay. When a viable implant remained in the anterior chamber, the spleen cells of these rats produced a popliteal lymph node enlargement in F1 hybrids which was approximately 50% of that produced by a similar number of cells from a normal animal. Conversely, the GVH response of spleen cells from orthotopically skin-grafted rats was noted to be significantly increased over the response of spleen cells from normal animals. The decrease in the GVH response of implanted rat spleen cells was a specific reaction and not because of trauma or implantation, since spleen cells from rats bearing syngeneic implants had shown no reduction in their GVH-inducing ability. The PLN weights of rats receiving mixed population of normal and implanted rat spleen cells were always less than the weights observed with an equal number of normal spleen cells. These findings permit the assumption that implant-bearing rats may be lacking or low in cells that induce GVH reactions or that there is a delayed conversion of effector cells after early immune recognition.


Specific suppression of graft-versus-host responsiveness by incubation of donor lymphoid cells with a solubilized membrane fraction of host lymphoid cells. BALB/c spleen cells were incubated with a solubilized membrane fraction (SMF) prepared from spleen and thymus cells of (BALB/c x C3H/He)F1 or (BALB/c x A/J)F1 hybrid mice. Cells incubated with (BALB/c x C3H/He)F1 SMF produced less graft-versus-host (GVH) splenomegaly in (BALB/c x C3H/He)F1 hosts than did untreated BALB/c cells. The reduction of GVH splenomegaly was specific, inasmuch as the GVH activity of (BALB/c x C3H/He)F1 SMF-treated and untreated cells was similar in (BALB/c x C57BL)F1 hosts, and BALB/c cells treated with (BALB/c x A/J)F1 SMF showed no alteration of GVH activity in either (BALB/c x C3H/He)F1 hosts or (BALB/c x C57BL) F1 hosts. The time course of splenomegaly did not differ for SMF-treated and untreated cells. Donor cells that were labeled with tritiated adenosine and treated with (BALB/c x C3H/He) F1 SMF produced a reduction in the amount of label appearing in (BALB/c x C3H/He)F1 host spleens but not in (BALB/c x C57BL)F1 host spleens. Mechanisms which could account for the ability of SMF to cause specific reductions in both GVH activity and host spleen labeling are discussed.


A new model of bilateral hemispheric ischemia in the unanesthetized rat. A new model of transient, bilateral hemispheric ischemia in the unanesthetized rat is described. During ether anesthesia the rat's vertebral arteries were electrocauterized through the alar foramina of the first cervical vertebra and reversible clasps placed loosely around the common carotid arteries. Twenty-four hr later, the awake rats were restrained and the carotid clasps tightened to produce 4-vessel occlusion. The carotid clasps were removed after 10, 20 or 30 min of 4-vessel occlusion and the animals killed by perfusion fixation 72 hr later. Rats which convulsed during the ischemic or post-ischemic period were excluded from further study. All rats subjected to 20 or 30 min of 4-vessel occlusion demonstrated ischemic neuronal damage. The H1 and paramedian hippocampus, striatum and layers 3, 5 and 6 of the posterior neocortex were the regions most frequently damaged. The advantages of this model are the ease of preparation of large numbers of animals, a high rate of predictable ischemic neuronal damage, a low incidence of seizures and the absence of anesthesia.


Lymphocyte traffic within the bone marrow and selective retention of alloreactive cells. Earlier studies showed that large numbers of isotopically labelled thoracic duct lymphocytes (TDLs) enter the bone marrow (BM) within hours of injection but depart equally as rapidly by 12 to 24 hr. The significance of this rapid flux was investigated further. Early (1/2 to 2 hr) after the i.v. injection of TDLs, BM was shown to contain T cells capable of initiating a graft-versus-host (GVH) reaction in F1 hybrids and in other experiments memory cells against human serum albumin (HSA). Both GVH and memory cell activity had markedly declined in the BM by 12 hr. In contrast to the rapid departure of TDLs from syngeneic BM, F1 hybrid BM retained parental lymphocytes with GVH activity for alloantigens of the opposite parent. F1 hybrid BM under these circumstances supported the transformation and proliferation of lymphocytes activated in situ by alloantigens. These selectively retained T cells also reacted to third-party alloantigens. In addition, TDLs with memory for HSA were retained in the BM of F1 hybrids. The BM is a site in which alloreactive immune responses may be initiated or sustained.


Survival of rabbits after prolonged cerebral ischemia. Cerebral ischemia was produced by a combination of vascular occlusion and mild systemic hypotension in 2 groups of rabbits. Arterial blood pressure, arterial pH, arterial blood gases, blood glucose and PCV were monitored and recorded before, during and for 3 hours after reperfusion. Return of EEG activity, vasomotor control, spontaneous ventilation and corneal reflex were also recorded. At 4, 8, 12, 24 and 48 hours after reperfusion, the rabbits' neurologic status was assessed according to an arbitrary scale based on motor function. The 2 groups differed in return of reflexes and motor function. Eighty percent of the rabbits ischemic for 20 minutes and 75% of the rabbits ischemic for 30 minutes survived. The graduated response of motor function to cerebral ischemia is attributed to the ventilatory and circulatory support given the rabbits for the first 3 hours after reperfusion. The graduate response of motor function to ischemia supports the suggestion that motor function can be used as an index of neurologic damage.


Correction of decreased guanylate cyclase activity in diabetic rats by pancreatic islet transplantation. We have previously demonstrated that streptozotocin-induced diabetic rats have decreased guanylate cyclase (EC 4.6.1.2) activity in liver and other tissues which was returned to normal by the administration of exogenous insulin. Since successful pancreatic islet transplants have been shown to lower basal hepatic glucose output, gluconeogenesis, and urea production, pancreatic islet transplants seemed to be a more physiological model to test the in vivo effects of insulin on guanylate cyclase activity in diabetic animals. The present investigation demonstrates that pancreatic islet transplants into two different species of streptozotocin-induced diabetic rats increased the lowered activity of guanylate cyclase activity found in diabetic animals to the level of guanylate cyclase activity present in control animals.


[Effect of different concentrations of HCO3- and CO2 in aquarium water on metabolism in the Cyprinus carpio L. organism]. The level of pCO2 and bicarbonates in blood and tissues of Cyprinus carpio L. increases with concentration of carbonic acid (HCO3- and pCO2), the other indices of the hydrochemical composition being constant. The value of blood pH is unchanged. In fish with a higher content of carbonic acid in blood the amount of lactate, pyruvate, oxaloacetate, malate, citrate, alpha-ketoglutarate, ammonia, glutamin, free amino acids, total and residual nitrogen rises. Simultaneously the content of urea increases in kidneys, but decrease in gills, whereas in blood and live it does not differ from the corresponding indices of fishes from the control group.


[Method for determining peroxidase activity]. The spectrophotometric method is described for the peroxidase activity determination which is based on the oxidation of guaicol and potassium iodide. Optimal conditions were elaborated for these two most sensitive substrates. The method may be applied for the quantitative peroxidase determination in different human biological fluids, in particular saliva and blood serum.


Microphallus: clinical and endocrinological characteristics. The clinical and endocrinological features of 15 male subjects with small but normally formed external genitalia are reviewed. Nine of these patients had a simple microphallus alone, while the other 6 patients exhibited associated central nervous system defects. The endocrine data obtained from both groups were the same and were consistent with defective hypothalamic function. Parenteral testosterone seems to be the present treatment of choice but we believe it should be started early in life to take advantage of the greater hyperplastic response of the young.


Clinical implications of gonadal venography in the management of the non-palpable undescended testis. Selective gonadal venography was used on 28 patients with a total of 34 non-palpable undescended testes. The data obtained in this study suggest that 1) an internal spermatic vein with a pampiniform-like plexus indicates the presence of a testis, 2) a blind-ending vein on venography suggests the absence of a testis, 3) an internal spermatic vein or vas deferens may be present without a testis, 4) a testis probably cannot be present without a gonadal vein, 5) a testis may be present without a vas, 6) a blind-ending vas deferens does not necessarily indicate the absence of a testis and 7) a blind-ending vas deferens in a patient in whom a blind-ending gonadal vein is localized to the same region probably indicates the absence of a testis. Gonadal venography may localize a non-palpable undescended testis or suggest testicular agenesis. In addition, gonadal venography has aided in the selection of the operative approach and, in the future, may provide criteria under specific circumstances for determining whether an operation is necessary and, if so, the extent of surgical exploration.


[Water intake, pH and ammonia levels in the ruminal contents of sheep fed pelleted feed]. Wethers were studied for the effect of the complete pelleted feed ration on the intake of water and concentration of pH and ammonia in the rumen. The animals consumed daily 1300 g of dry matter of the diet containing 41.81% of meadow hay, 25.8% of barley, 15.37% of sawdust, 14.98% of molasses, 1.32% of urea and 1.24% of vitamin mineral supplement. This feed was given to them for six months. The pelleted diet increased the intake of water (the dry matter consumption remaining the same in the control and experimental group), reduced pH concentration (6.0--6.2) and slightly increased the level of ammonia in the first hour after feeding; this was probably due to a rapid release of nitrogen compounds from the feed and to intensive rumen fermentation.


[Dynamics of acid-base indices in the blood of lambs from the 7th day of postnatal life to adult age]. Under the conditions of a specialized farm equipped with amodern technology or rearing, sixteen ewe lambs of the Improved Wallachian breed were studied for the dynamics of acid-base indices in the blood from the seventh day of post-natal life unitl the age of 19 months. The acid-base parameters were measured by the Astrup BMS 2 apparatus. After weaning at an age of 45 days, the lambs were fed mixture COJ 1 for ten days, then mixture COJ 2, followed by the administration of a VJ mixture and granular feed in a 1 : 1 ratio. The mentioned feeds were given to the lambs ad libitum. At the beginning of July the animals were driven to pasture where they were kept with no supplementary feeding. In the winter season they were kept indoors and were fed briquettes of forage at a ration of 2.3 kg per head per day. In the second year of age the sheep were driven to pasture in early. May. Throughout the period of study, the values of actual pH in the blood ranged ranged from 7.29 to 7.39 and pCO2 from 4.33 to 6.25 kPa, on an average; BE ranged from -8.2 to -1.8 mmol 1(-1), BB from 35.7 to 49.3 mmol 1(-1), and SB had limiting means of 18.0 and 22.7 mmol 1(-1), AB 16.7 and 23.5 mmol 1(-1), and tCO2 ranged from 17.7 to 24.8 mmol 1(-1), on an average. The highest numerical fluctuations in the values of the indices under study were recorded in the period of transition to the different kinds of solid feeds and to pasture.


Hairy cell leukemia: differences in phagocytic capacity of cells in vitro. Hairy cells from eight patients with hairy cell leukemia were evaluated with both light and transmission electron microscopy for their capacity to phagocytose zymosan, latex, staphylococcus aureus, and pseudomonas aeruginosa. In two patients, there was no phagocytosis of any of these substances; cells from three patients phagocytosed only latex; two, all except pseudomonas; and one, all 4 substances. Hairy cells became relatively smooth while in culture with staphylococcus, but no surface changes were noted during incubation with the other substances. Of the eight patients studied, one died of pseudomonas pneumonia and sepsis; pseudomonas was the only substance which her hairy cells did not phagocytose. The one patient whose hairy cells phagocytosed all 4 test substances developed a disseminated Mycobacterium intracellulare infection; culture of his hairy cells with this atypical myocbacterium showed no phagocytosis. Hairy cells have different phagocytic capabilities from patient to patient, and the evaluation of these capabilities in vitro might provide early identification of potential infectious complications.


Invasion of malignant C3H mouse fibroblasts from aggregates transplanted into the auricles of syngenic mice. Spheroid aggregates of malignant fibroblasts (MO4), shown to be invasive in vitro, were implanted subcutaneously into the auricle of the external ear of syngenic C3H mice. The course of early invasion into the surrounding tissues and the formation of tumours was studied in serial sections of auricles fixed 6 h to 30 days after implantation. MO4 cells are first observed to make contact with the surrounding tissues after 6 h. They exhibit, cytoplasmic extensions and spread from the original aggregate. During the first day invading MO4 cells preferentially follow tissue crevices created by the inoculation procedure. Later they also invade the surrounding tissues. Polymorphonuclear leucocytes, and later monocytes infiltrate the aggregate, which is completely destroyed after 4 days. Palpable tumours arise from MO4 cells that have left the original implant and invaded the tissues of the auricles. These observations indicate that invasion of malignant cells is important for the take of a transplant.


Selective lesions of acinar pancreatic cells in rats poisoned with abrin. A morphological and biochemical study. Rats poisoned with abrin (2.5 micrograms/100 g body weight) died within 36 h with severe necrosis of acinar pancreatic cells. Incorporation in vivo of labelled amino acids into pancreatic protein was greatly impaired 6 h after poisoning. Microsomes isolated from the pancreas of poisoned rats at 6 h had a reduced capacity for protein synthesis in vitro. Incorporation in vivo of orotic acid into pancreatic RNA was decreased 12 h after poisoning.


The mechanism of epithelial shedding after ischemic damage to the small intestinal mucosa. A light and electron microscopic investigation. The intestinal mucosa of the rat was examined by light and electron microscopy 15, 30, 60 and 120 min after complete ligation of the vessel arcades of the proximal jejunum. The characteristic sign of ischemic damage to the small intestinal mucosa and the reason for epithelial shedding is the appearance of membrane enclosed cytoplasmic blebs which arise at the cell base of the enterocytes and detach the epithelium from the basement membrane. This process begins at the tip of the villi before the enterocytes display signs of irreversible damage and progress to the base of the villi with continuation of the ischemia.


The carcinogenic effect of TPA (12-0-tetradecanoylphorbol-13-acetate) when applied to the skin of hairless mice. Groups of hairless mice received one, two, five and fifty applications of 20 nmoles TPA (12-0-tetradecanoylphorbol-13-acetate) on the skin of the back, and were observed for 20 months. The animals developed some papillomas, some squamous cell carcinomas, some fibrosarcomas of the dermis, and some malignant and benign tumours in internal organs. There was a small, not significantly different, incidence of benign and malignant tumours after 1, 2 and 5 paintings, and a significantly higher tumour incidence after 50 applications. Apart from reticuloses, which are commonly seen in these animals, the occurrence of other tumours is believed to be related to the TPA treatment. The results are interpreted as showing that TPA, like croton oil, should be regarded as a complete carcinogen.


Asynchrony of erythroblast maturation induced by riboflavin deficiency. Ultrastructural studies indicate that galactoflavin-induced riboflavin deficiency induces asynchrony of rat erythroblast maturation. During the latter stages of maturation erythroblasts retain significantly larger numbers of ribosomes as compared to control cells. Nucleoli are not evident in erythroblasts whose nuclei indicate cells in the latter stages of development. Membrane whorls develop within the mitochondria of plasma cells, eosinophils and neutrophils during the fifth week of riboflavin deficiency. No further evidence of degeneration was noted among additional cell organelles.


Electron microscopic morphometric analysis of small cortical and medullary thymocytes from the rat. Electron microscopic morphometric analysis of rat small thymocytes reveals quantitative differences between small cortical and medullary thymocytes. The unit gravity velocity sedimentation technique was used to obtain a cellular pool composed mainly of small sized thymocytes. Stimulation "in vitro" with phytohemagglutinin followed by cell size separation was employed to separate cortical small thymocytes. Furthermore, isolation of medullary small thymocytes was carried out by treatment "in vivo" with hydrocortisone. Our results show that the majority of the quantitative changes correspond to differences in the distribution of chromatin and the density of perichromatin granules. They demonstrate the importance of chromatin pattern analysis for the identification of small cortical and medullary thymocytes.


Flow cytofluorometric analysis of a human aneuploid cell line growing in vitro and in intraperitoneal diffusion-chambers. An aneuploid established cell line originating from human skin (NCTC 3075) was cultivated in vitro culture and in intraperitoneal diffusion chambers in hamsters. In in vitro cell culture a near tetraploid cell line dominated. Shortly after implantation into the diffusion chambers in the peritoneal cavity of hamsters a selective lysis of cells with near tetraploid DNA content occurred, with a relative increase of a diploid subline. After 5 days in the hamster a tetraploid cell line again dominated as in in vitro culture. The use of flow cytofluorometry for ploidy analysis and changes in cell cycle traverse is demonstrated. The possible use of this model system in studies of response to therapy is discussed.


Epithelial cell kinetics in the descending colon of the rat. Epithelial cell kinetics were investigated in the descending colon of the rat. The number of cells per crypt was found to be approximately 625, with 33 cells per cell column and 19 cell columns per crypt circumference. The growth fraction of the colonic crypt was 0.42, and proliferating cells were situated largely in the lower half of the crypt. The cell cycle time was 50.5 h, with values for the G1, S and G2 phases of 40.0, 7.6 and 2.9 h respectively. Cell migration studies showed that it took 60-72 h for a cell to migrate from the upper border of the proliferative cell compartment in the crypt to the luminal surface of the colon. Data were also obtained from continuous labelling with tritiated thymidine and from studying the circadian rhythm of proliferative activity, which suggest that the cells in the bottom of the crypt may constitute a separate, more slowly cycling (stem)cell compartment.


Methods of study of the invasion of malignant C3H-mouse fibroblasts into embryonic chick heart in vitro. Methods of study of tumour invasiveness in vitro were investigated using the interactions between malignant virally transformed C3H mouse fibroblasts (MO4) with fragments from embryonic chick heart. Invasion of MO4 cells into the heart tissue could be demonstrated in all three-dimensional cultures. On the contrary, seeding of MO4 cells on top of a monolayer of heart cells did not mimic invasion. Precultured heart fragments were more suitable for the study of the early phase of invasion than freshly cut ones because they presented healthy well-delineated borders. Aggregates of MO4 cells proved more suitable than suspensions or monolayer fragments because they were amenable to quantitation, were not traumatized or treated with enzymes during harvest. They allowed precise control of the initial site of contact with the heart tissue. The nature of the culture medium predominantly affected the growth of the MO4 population. This factor influenced the pattern of invasion quantitatively, but did not alter the invasive capacity of the MO4 cells itself. In cultures on adhesive substrates the interaction between the MO4 cells and the heart tissue was complicated by the fact that both also interacted with the aritficial substrate. Shaker cultures appeared better than comparable static cultures because they allowed better aeration and so delayed central necrosis.


[Transplantability and growth of sarcoma 37 under a ganglionic blockade]. The inoculation of sarcoma-37 against the background of the ganglionary blockade, provided by the intraperitoneal injection of 1 ml of pentamine, is not associated with its less take rate, but there is a manifest suppression of the tumor growth during the period up to 63 days. A preliminary ganglionary blockade completely eliminates the stimulating effect of a trauma on the tumor growth.


Incompatibility in vitro and in vivo demonstrated only with saline-suspended red cells. An unusual IgG complement-binding antibody was observed in a 64-year-old man prior to surgery. This antibody was detectable by the indirect antiglobulin test when the red cells were suspended in saline, but not when they were suspended in acid citrate dextrose or albumin solutions. Positive reactions were obtained with the patient's own red cells and with the cells of all donors tested. In vivo chromium survival studies showed that donor cells and patient cells, when suspended in saline, had 1-hour survivals of 32 and 46%, respectively. In contrast, donor and patient cells suspended in ACD solution had 1-hour survivals of 77 and 93%, respectively. We concluded that this phenomenon may casue accelerated destruction of saline-suspended cells and should be suspected whenever in vitro incompatibility is noted with red cells suspended in saline.


[Comparative studies of hemoglobin methods for the determination of blood hemoglobin concentration]. The interference and clarifying effect of the non-ion detergents "Vero" "Verolux", "Alva" and "Alkaryl" on the formation of cyanhemiglobin and azihemiglobin complexes in slightly alkaline media (pH 7.2) (methods of von Kampen and Zijlstra and of Vancetti and Nardeschi) are studied by the investigation of standard curves, spectral characteristics of colour complex and time effect. The high degree of correlation (r = +0.960 to +0.999) with the parallel investigations with Nonidet P 40 and the negligible interference of the detergents studied provide grounds to substitute Nonidet P 40 in the recommended prescriptions for the preparation of transforming solutions for "Vero", "Verolux", "Alva" and "Aklaryl", especially if some of them (for instance Vero) is prepared with a purity degree, meeting the analytical needs of laboratory practice.


[Clinical chemical parameter changes in patients with liver metastases]. Certain biochemical serum parameters: GOT, GPT, LAP, HK, AP and Regan isoenzyme, GGTP, CE, ESR, Weltman test, thymol test, serum bilirubin and urine urobilogen were determined in 39 patients with different localization of malignant processes in the abdominal cavity (stomach, large intestines, pancreas, ovaries). The patients were subdivided into two groups, depending on the presence or absence of liver metastases, confirmed at laparatomy, laparascopy or necropsy material examination. The results revealed that in patients with liver metastases AP, CE, GOT, GGTP, ESR and Weltman test are most commonly and simultaneously abnormal. In patients without liver metastases, those indices are also changed but to a lesser degree, whereas LAP and Regan isoenyzme are with elevated activity in a higher per cent of these cases, than in the patients with liver metastases, being in unison with literature data. The determination of the above biochemical parameters could direct the clinicist to the presence of liver metastases but the more reliable diagnostic methods as laparascopy and laparatomy cannot be substituted for.


[The unaffected primary rejection of xenogeneic kidney transplants in the closely related fox-dog species system]. The present study reports of three kinds of experiments of unaffected primary rejection of xenogenous kidney transplanats in the close-related fox-dog species system. The issue is whether there is a relation between the amount of grafted parenchyma and the immune induced potency, that is whether the course of rejection of transplanted single kidneys (group I a) differs from the course after en-bloc transplantation of both kidneys (group I b). In group II alterations of blood chemism and behavior of humoral antibodies are followed in dogs to which a fox kidney was transplanted, while keeping their own functioning kidneys. This experiment is to give information whether the uremic syndrome influences the development of humoral immunity, and what changes of blood chemism may primarily be related to destruction of the graft, under the condition of absent uremia. Untreated graft recipients survived for 5,4 +/- 0,49 days (n = 5) when single kidneys were transplanted (group I a), and 5,2 +/- 0,75 days (n = 5) when both kidneys were grafted en-bloc (group I b). As to the rejecting reactions, both groups are almost equal: the increasing functional failure causes a fast increase of creatinine and urea nitrogen; alkaline phosphatase and LDH show distinct alterations, related to the progress of the graft's destruction. Decrease of albumin level and loss of cholinesterase activity indicate an impaired hepatic function as reaction to uremic intoxication. Gamma-globulins and leucocytes show alterations that can be related to non-specific inflammatory reactions. The immunologically specific initial lymphopenia suggests that after revascularization these cells migrate to the graft, and later react with antigenic structures of vascular endothelium and still later with those of the organ cells. Cytotoxic antibodies appear on the 4th postoperative day in increasing amount. Post mortem histologic examination shows round cell infiltrates in the vastly necrotic renal parenchyma. When the recipient's kidneys are kept in situ and a fox kidney is transplanted (group II) uremia is avoided and the animals survive. During the 30-days period of observation, that is longer than the term of rejection, the titer of cytotoxic antibodies remains stable or tends to increase. LDH and alkaline phosphatase show characteristic changes that are considered sequels from destructed transplantate. The experiments show, aside from certain reservations, that the donor-host combination fox-dog is suitable to serve as preclinic model for human transplantation using xenogenous donors of organs, i. e. anthropoid primates.


[Pathology of pulmonary changes in Wegener's granulomatosis, rheumatoid arthritis and polyarteritis nodosa (author's transl)]. Histology of the pulmonary alterations which may occur in Wegener's granulomatosis, rheumatoid arthritis and polyarteritis nodosa is enumerated. 30 own cases with pulmonary lesions are presented. The difficulties of differential diagnosis in lung biopsies are discussed. Both Wegener's granulomatosis and rheumatoid arthritis may terminate in a generalized necrotizing arteritis which cannot be distinguished from polyarteritis nodosa. This as well as various other similarities indicate that these three different disease entities base on an identical hyperergic reaction of the vascular wall. Only the so-called limited type of Wegener's granulomatosis has a relatively favourable prognosis.


[Metabolism of dicarboxylic amino acids and their amides in bacteria of the genus Citrobacter]. In 58 Citrobacter strains the pathways of the utilization of dicarbonic amino acids and their amides were studied. These organisms were found to be incapable of decarboxylating glutaminic and asparaginic acids, as well as their amides. All the strains could actively desamidizate asparagine. Not all of these strains showed glutaminase activity. Aspartate-aminotransferase occurred twice as often as alanine-aminotransferase, the level of activity being approximately the same. The Citrobacter strains desamidizated asparaginic acid with great constancy, but only in 1/3 of them this reaction occurred via an aspartase route. The desamidization of asparaginic acid in Citrobacter seemed to proceed in different ways. The desamidization of glutaminic acid was observed only in a part of the strains, and the reaction proceeded less actively.