Erythropoietin, thrombopoietin and colony stimulating factor in fetal mouse liver culture media. Fetal mouse livers, days 13 to 19 of gestation, were cultured for 21 days and the culture media tested for erythropoietin (Ep), thrombopoietin (TSF) and colony stimulating factor (CSF). High levels of both Ep and CSF were released into the culture media. However, no detectable TSF was found. Maximum Ep culture activity was detected in day 14 and day 15 fetal liver cultures while maximum CSF was found in the day 16 fetal liver culture. These studies indicate that fetal liver cells in culture are capable of producing and/or releasing both Ep and CSF but not TSF.


Histiocytosis X in adult with skin and uncommon central nervous system involvement. Report of a case of histiocytosis X with adult onset, widespread skin lesions and rare central nervous system involvement resulting in dizziness and ataxia. On autopsy histiocytosis X infiltrates in the central nervous system were demonstrated with granuloma formation in the temporal lobe and nucleus dentatus of the cerebellum.


[Effect of methotrexate on the level of T- and B-lymphocytes]. Through an analysis of the immune response of mice to sheep's erythrocytes within a system of syngenic transfer the action of Methotrexate on the T- and B-lymphocytes was studied. Splenic cells of donors receiving methotrexate were introduced to lethally irradiated recipients together with the bone morrow or thymus cells. In the recipients' spleen the content of antibody-forming cells and hemolytic foci were determined. It was shown that in recipients receiving splenic cells alone the number of antibody-forming cells and of the foci sharply declined under the effect of methotrexate. Introduction of the bone marrow cells contributed to reconstitution of the response in recipients at the level of the antibody-forming cells, but not at that of the hemolytic foci. At the same time, thymocytes increased the content of the antibody-forming cells up to a level exceeding the control one, as well as the number of foci. The results proof methotrexate capable of inhibiting the proliferation of the T- and B-cells in the spleen of mice, induced by the antigen.


[Effect of contrical introduced into Wirsung's duct on the morphofunctional response of the pancreas in acute experimental pancreatitis]. Induction of contrical into Wirsung's duct is shown to lessen the total proteolytic amylolytic and lipolytic action of the pancreatic juice, blood and urine, normalizing by this token the exo- and endosecretion of the pancreas. It is also shown that in acute pancreatitis there is in evidence hyperfunction of the acinar glandular cells, responsible for the synthesis of the secretion, and their focal destruction. Introduction of contrical into Wirsung's duct degrades intracellular processes of the secretion synthesis.


Chloride transport and acid secretion in stomach. Chloride transport in isolated frog gastric mucosa is known to include major components due to active transport and exchange diffusion, and a minor component due to passive diffusion, but the sites responsible for moving Cl- within the mucosa have not been identified. The present study shows that the method used by Zerahn and others to measure transport pool yields an apparent Cl- pool which is close to the Cl- content of mucosal cells measured by chemical or radioactive means. Uptake of Cl- by the mucosal cells across the luminal surface in 2 min is rapid, constituting over one-half of the steady state cell content. The results suggest that much of this uptake occurs by exchange diffusion of Cl- at the secretory surface.


An attempt to correlate functional and morphological data for the gastric parietal cells. In fed rats, acid production was estimated to be 7 X 10(8) molecules of HCl per cell per sec or 5 X 10(5) molecules per sec per mu2 of secretory surface. In stimulated frog mucosa the corresponding values were 3 X 10(8) molecules of HCl per cell per sec 2 X 10(5) molecules per sec per mu2 or secretory surface. The generous assumptions used in making these estimates could have led to large errors.


Effect of acetylsalicylic acid on gastric mucosa. II. Mucosal ATP and phosphocreatine content, and salicylate effects on mitochondrial metabolism. The effects of acetylsalicylic acid on gastric mucosal ATP and phosphocreatine and mucosal O2 consumption were studied using in vitro bullfrog gastric mucosa. Electrophysiological parameters (potential difference and resistance) changed rapidly after exposure to 10 or 20 mM acetylsalicylic acid at pH 3.0, 4.0, or 6.0 in the mucosal solution. ATP and phosphocreatine content decreased rapidly after exposure. Control mucosae contained 11.8 +/- 0.98 nmoles of ATP and 11.5 +/- 0.68 nmoles of phosphocreatine per mg of protein. ATP content decreased 21% and phosphocreatine decreased 45% after 15 to 30 min of exposure. Longer durations of exposure reduced both ATP and phosphocreatine to 10 to 15% of control levels. O2 consumption was increased during the first 15 to 30 min after exposure to acetylsalicylate. Longer durations of exposure reduced O2 consumption to near control levels. Study of isolated mitochondria confirmed that acetylsalicylate itself did not significantly affect mitochondrial respiration, respiratory control ratio, or ADP:O ratio. Salicylate had a biphasic effect which was concentration dependent. Salicylate initially stimulated and later inhibited mitochondrial respiration. Using various substrates the site of inhibition appeared to be located in the segment of the respiratory chain between coenzyme Q and cytochrome c1.


[Dosis-performace-effects on the pluripotent hematopoietic stem cell. Results of partial body irradiation using 8MeV-x rays]. It was the aim of this study of document the influence of various dose rates on the CFU'S compartment. The information obtained should serve as a guideline to the design of radiotherapeutic programs with less hemopoietic toxicity in clinical radiation therapy. CBA mice were subjected to partial body X-ray irradiation from a linear accelerator (8MeV). The effect of dose rates of 6,70, 520 and 2800 R/min on CFU'S were studied in the irradiated and shielded marrow immediately after irradiation and 5,24 resp. 48 hours, 1 week and 3 weeks later. The following conclusions can be made: The reduction of CFU'S is significantly greater for low dose rates. After a dose of 150 R CFU'S reach normal values at 2 weeks, after 300 R at 3 weeks. With 450 R they are still subnormal at 3 weeks. A rebound phenomenon with increased CFU'S is seen at 3 weeks with 150 R and 300 R. An increase of CFU'S in shielded marrow is seen immediately after irradation. This increase is not dependent on the dose rate. The clinical implications of these findings are discussed.


Inbreeding in recessive diseases.

Inbreeding in recessive diseases. The consanguinity of parents (born in France) of individuals who have a recessive disease has been studied. The frequency of first cousin marriages is less than 0.2% in the general French population. Among the parents of affected individuals the following frequencies of first cousin matings were observed: cystic fibrosis: 1.4% cystinosis: 7.1% nephronophtisis: 5.6% spinal muscular atrophy: 4.5% albinism: 5.0% achromatopsia: 12.5% (Albinism and spinal muscular atrophy are heterogeneous conditions). The increase in the frequency of first cousin marriage relative to that of the general population is much greater, as expected, in cystinosis, which is a rare disease, than in cystic fibrosis, which is the most frequent recessive disorder in France. Inbreeding in cystinosis and cystic fibrosis was also studied by computing the distance between parental birth places. This distance is smaller in cystinosis than in cystic fibrosis.


Non-specific factor replaces T cells in an IgG response to soluble antigens. The antigen and T-cell requirements for the final stages of proliferation and maturation of DNP-KLH primed and boosted mouse spleen cells into IgG antibody secreting cells have been studied in vitro. The requirement for free antigen ceases after 24-48 h in vitro. The carrier-specific T-cell requirement for triggering of activated B cells by a soluble antigen (DNP-KLH) can be replaced in T cell-depleted cultures by non-antigen specific T cell-replacing factors (TRF). However, if the carrier protein is changed, TRF restores the IgG response of T cell-depleted cultures only if antigen is presented to B cells in particulate form, e.g. on the surface of macrophages, or in the presence of small amounts of antibody against the carrier protein. Thus, direct interaction between soluble protein and B cells is not sufficient to allow TRF to effectively replace specific T cells. Since TRF must be added at the start of culture, the initiation of B-cell maturation into IgG secretion by TRF occurs during B-cell proliferation, and is followed by further proliferation before IgG antibody can be detected.


Two subpopulations of guinea-pig thymocytes with different maturation stages. Two subpopulations (F4 and F6) of guinea-pig thymocytes were separated by using bovine serum albumin gradient centrifugation. The majority of F4 thymocytes were weakly alkaline phosphatase (AP) positive cells, while most of F6 thymocytes were strongly AP positive. The significant difference between their AP activities was confirmed biochemically. In the ultracytochemical study the majority of unfractionated and F6 thymocytes were light and AP positive, whereas F4 thymocytes were mostly dark, weakly AP positive cells. F4 thymocytes responded well to PHA and Con A, while F6 thymocytes failed to respond to these mitogens. The subpopulations did not differ in their homing properties. These findings indicate that strongly AP-positive cells are immature thymocytes and weakly AP-positive cells represent a more mature subpopulation of thymocytes. A hypothetical scheme for differentiation of guinea-pig thymocytes is presented.


A suppressor mechanism controlling lymphocyte recruitment. The duration of the inductive effect of an antigen (alum-precipitated trinitrophenyl-keyhole limpet haemocyanin) was measured, in the presence and absence of responding spleen cells, by transfering a test population of spleen cells to irradiated mice at various times relative to antigen injection. Using allotype-congenic mice, the response of a test (Iga) population was estimated in the presence of responding (Igb) cells. In the absence of responding cells the inductive effect fell to 10% of the peak value in 9-10 days, but in their presence it reached this level in less than 5 days. Removal of T cells from the responding (Igb) population reduced their suppressive efficacy. It was concluded that B lymphocyte recruitment is curtailed not by the elimination of antigen but by an active suppressor mechanism involving suppressor T cells.


Mechanism of adjuvant activity of dental plaque: in vitro activation of residual helper T-cell precursors in T-cell-deficient murine spleen cell cultures. The immunoenhancing activity of a water-soluble extract of dental plaque (DP), which contains a mixture of microbial antigens, has been investigated. DP was tested for its capacity to augment the in vitro antibody-forming cell (AFC) response to sheep erythrocyte by adherent spleen cells from thymectomized, lethally irradiated, and bone marrow-transplanted (TxB) mice. Although DP was found to induce a small polyclonal AFC response, most of the increase in AFC induced by DP was antigen dependent. The latter enhancing effect is an indicator of the adjuvanticity of DP. This adjuvant activity of DP was T-cell-dependent, since removal of the residual prethymic and/or thymic-derived lymphocytes (T-cells) by anti-T-cell serum (anti-theta) and guinea pig complement abrogated the capacity of DP to augment the in vitro AFC response. This view was further supported by the synergistic restorative effect obtained by culturing anti-theta-treated adherent spleen cells with both DP and a population of unactivated T-cells that by themselves were unable to significantly enhance AFC responsiveness. Moreover, DP was found to be mitogenic for thymocytes. The cumulative results suggest that the adjuvant activity of DP is dependent on both the T- and B-cell-activating components present in DP.


Cell-mediated immunity to tumor antigen in Marek's disease: susceptibility of effector cells to antithymocyte serum and enhancement of cytotoxic activity by Vibrio cholerae neuraminidase. Spleen cells from chickens inoculated 7 to 8 days previously with Marek's disease virus were cytotoxic for 51Cr-labeled cells of a Marek's disease lymphoblastoid cell line (MSB-1 line) in a 4-h in vitro cytotoxic assay. The cytotoxic activity of spleen cells was inhibited by pretreatment with antithymocyte serum and complement, but not with complement alone or in combination with anti-bursa cell serum or normal preimmune serum. The conclusion was that the effector cell in the above cytotoxic assay was a thymus-derived lymphocyte. Also, pretreatment of target cells with Vibrio cholerae neuraminidase enhanced in vitro cytotoxic activity of effector cells. Similar enzymatic treatment of effector cells had a negligible effect on cytotoxicity.


Polyribosome distribution in regenerating livers of irradiated adrenalectomized rats. The effect of gamma-radiation (1800 rad) on polyribosome distribution in the regenerating livers of intact and adrenalectomized rats was studied both before and after partial hepatectomy. The animals were divided into four sub-groups: (1) control; (2) irradiated only; (3) partially hepatectomized; and (4) irradiated partially hepatectomized. The relative distribution of lighter oligosomes to heavier polyribosomes was analysed by sucrose density gradient centrifugation (10-40 per cent). Partial hepatectomy by itself increased the proportion of heavier polyribosomes in both intact and adrenalectomized rats. However, when gamma-rays were delivered 2 hours before or 2 hours after partial-hepatectomy, the formation of heavy polyribosomes was decreased for at least 24 hours after hepatectomy in the adrenal intact rats. This depression was not maintained until later times (48 and 72 hours after hepatectomy) when an increase in the proportion of heavy polyribosomes relative to light oligosomes was observed. In addition, irradiation did not measurably affect the distribution of polyribosomes in regenerating hepatocytes of adrenalectomized rats at any time after partial hepatectomy.


Plutonium in bone: a high resolution autoradiographic study using plutonium-241. Plutonium-241 citrate solution at pH 6-5 was injected intravenously into hamsters and an adult rabbit at a dose of 10 kBq g-1 (260 nCi g-1). The hamsters were killed serially at 15 min, 2 hours, 1 day, 10 days, 1 month and 6 months after injection and the rabbit at 1 week. Their knee-joints or femora were examined for plutonium-241 by autoradiography. Few differences were found between the pattern of plutonium distribution in the hamsters and the rabbit. The results showed that although plutonium is initially distributed on bone surfaces, at long periods after injection it becomes deposited throughout the bone matrix. Plutonium uptake by cells in resorbing areas of periosteum, in active osteoblasts, and in chondrocytes in regions of cartilage mineralization was rapid. Plutonium concentrated more slowly on the resting bone surfaces and at sites of low metabolic activity. In addition, some unlabelled sections of skeletal tissues were immersed in a plutonium-241 citrate solution. When autoradiographed, it was found that plutonium was bound by cell nuclei, tooth enamel matrix, dentine, predentine and bone matrix. Plutonium binding to cartilage matrix was weak. The results are discussed with reference to the literature, and a model is proposed to explain the distribution pattern and fate of plutonium deposits in bone.


Effects of 60Co gamma-irradiation on chondromucoprotein. Pulse radiolysis and 60Co gamma-radiolysis have been used to study the effects of ionizing radiations on the protein-polysaccharide complex, chondromucoprotein. Both hydroxyl radicals and hydrated electrons readily react with the complex, with second-order rate-constants of 4-55 X 10(8)M-1s-1, respectively. Depolymerization of the carbohydrate component, which is initiated by reaction of OH, readily occurs after irradiation in aqueous solution, as is evidenced by an increase in the formation of reducing-end groups and a decrease in the viscosity of the solution. The ability of the anionic carbohydrate component to bind cationic counter-ions also decreases.


The effect of gamma-radiation on the interaction of DNA with nuclear non-histone proteins. The interaction of nuclear sap proteins and chromatin non-histone proteins with DNA was studied by two methods: membrane filter technique and chromatography of 32P-labelled proteins on DNA-containing columns. Irradiated DNA binds a slightly greater amount of these proteins and much more firmly than the native DNA. The effect is caused by the appearance of the locally denatured sites in irradiated DNA. Irradiation of non-histone proteins disturbs their specific interaction with DNA more easily than the non-specific binding.


[Permanent nail changes following gold therapy]. Following gold therapy in a patient with rheumatoid arthritis a transient rash and permanent nail dystrophy resulted. Following onycholysis of several finger and toe nails the nails showed permanent alterations in form of longitudinal streaks and were extremely thin, soft, and fragile. Intracutaneous tests with the commercial gold solution revealed an allergic reaction of the delayed type.


A comparison of the responses of cultured myoblasts and chondrocytes to fibroblast and epidermal growth factors. The effects of fibroblast and epidermal growth factors on proliferation and differentiation of cultured myoblasts and chondrocytes have been compared. FGF stimulated myoblast proliferation, as determined by monitoring levels of DNA synthesis during seven days growth in vitro and by the morphology of the cultures after myotube formation. EGF has relatively little effect on myoblast proliferation. With chondrocytes, both FGF and EGF are mitogenic and FGF's, but not EGF's effect is potentiated by dexamethasone. One implication of these results is that in the course of differentiation cell types which develop from the same embryonic origin as fibroblasts are controlled by different sets of mitogenic factors. Myoblasts become primarily dependent on mitogenic agents such as FGF while chondrocytes can respond to both FGF and EGF.


Elemental distribution in striated muscle and the effects of hypertonicity. Electron probe analysis of cryo sections. A method of rapid freezing in supercooled Freon 22 (monochlorodifluoromethane) followed by cryoultramicrotomy is described and shown to yield ultrathin sections in which both the cellular ultrastructure and the distribution of diffusible ions across the cell membrane are preserved and intracellular compartmentalization of diffusabler ions can be quantitated. Quantitative electron probe analysis (Shuman, H., A.V. Somlyo, and A.P. Somlyo. 1976. Ultramicros. 1:317-339.) of freeze-dried ultrathin cryto sections was found to provide a valid measure of the composition of cells and cellular organelles and was used to determine the ionic composition of the in situ terminal cisternae of the sarcoplasmic reticulum (SR), the distribution of CI in skeletal muscle, and the effects of hypertonic solutions on the subcellular composition if striated muscle. There was no evidence of sequestered CI in the terminal cisternae of resting muscles, although calcium (66mmol/kg dry wt +/- 4.6 SE) was detected. The values of [C1](i) determined with small (50-100 nm) diameter probes over cytoplasm excluding organelles over nuclei or terminal cisternae were not significantly different. Mitochondria partially excluded C1, with a cytoplasmic/ mitochondrial Ci ratio of 2.4 +/- 0.88 SD. The elemental concentrations (mmol/kg dry wt +/- SD) of muscle fibers measured with 0.5-9-mum diameter electron probes in normal frog striated muscle were: P, 302 +/- 4.3; S, 189 +/- 2.9;C1, 24 +/- 1.1;K, 404 +/- 4.3, and Mg, 39 +/- 2.1. It is concluded that: (a) in normal muscle the "excess CI" measured with previous bulk chemical analyses and flux studies is not compartmentalized in the SR or in other cellular organelles, and (b) the cytoplasmic C1 in low [K](0) solutions exceeds that predicted by a passive electrochemical distribution. Hypertonic 2.2 X NaCl, 2.5 X sucrose, or 2.2 X Na isethionate produced: (a) swollen vacuoles, frequently paired, adjacent to the Z lines and containing significantly higher than cytoplasmic concentrations of Na and Cl or S (isethionate), but no detectable Ca, and (b) granules of Ca, Mg, and P = approximately (6 Ca + 1 Mg)/6P in the longitudinal SR. It is concluded that hypertonicity produces compartmentalized domains of extracellular solutes within the muscle fibers and translocates Ca into the longitudinal tubules.


Accelerated calcium ion uptake in murine thymocytes induced by concanavalin A. The mechanism of enhancement of Ca2+ uptake by the T cell mitogen concanavalin A (Con A) was studied in murine thymocytes. Native Con A enhanced the rate of Ca2+ uptake as much as 9-fold, an increase being observed within five minutes after Con A addition. The effect of Con A was reversed completely by alpha-methyl mannopyranoside (alpha-MM). Increased Ca2+ uptake was observed with increasing concentrations of Con A, between 2 and 400 microgram/ml, indicating that the stimulation of Ca2+ uptake is not restricted to mitogenic lectin concentrations (0.5-2 microgram/ml). Succinyl Con A exhibits only a slight effect in the same concentration ranges as native Con A. Ca2+ uptake, both in the absence and presence of Con A, is strongly dependent on energy metabolism and is carrier mediated. The augmentation of Ca2+ uptake by native Con A is due to an enhanced Vmax. Uptake of the anion, CrO42-, by thymocytes, found to be a non-saturable process, was also enhanced by Con A. The effect of Con A on CrO42- permeability appears to be independent of its effect on Ca2+ uptake.


Effect of 1-5 hydroxytryptophan infusion on growth hormone and prolactin secretion in man. The effect of a new soluble ester of 1-5 hydroxytryptophan (1-5 HTP, Ro 3-5940, 200 mg infusion) on prolactin (PRL) and growth hormone (GH) release was tested in 11 young, healthy subjects (6 men, 5 women). To minimize side-effects, peripheral decarboxylase inhibition was achieved with benserazide (Ro 4-4602.) PRL increased significantly (P less than 0.01) after benserazide alone in all subjects. A further significant increase (P less than 0.01) of PRL plasma levels occurred only in women up to 90 min after the infusion of 1-5 HTP was discontinued. Benserazide administration had no effect of basal GH levels, but a significant increase of GH release (P less than 0.01) was noticed 30-120 min after the end of 1-5 HTP infusion in both men and women. The mean peak value of GH plasma levels after 1-5 HTP administration was 32.0 +/- 8.8 ng/ml. It was postulated that benserazide penetrated at the level of the pituitary, decreasing the synthesis of dopamine and consequently reducing its known inhibitory effect on PRL release. The PRL increase (statistically significant only in women), as well as the release of GH after 1-5 HTP infusion, was considered as further evidence for stimulatory serotoninergic control of both PRL and GH secretion.


Cytoarchitectonic analysis of the bullfrog (Rana catesbeiana) spinal cord by means of electron microscopy with special reference to distribution of microneurons. In order to determine cytological nature of the "small cells" found in the dorsal half of the bullfrog spinal cord at the electron microscopic level, the complete mapping of these elements was carried out, using both paraffin and thick sections. As a result, these elements were demonstrated to have four main fine structural characteristics of an unequivocally neuronal nature: (1) synaptic contacts, (2) subsurface cisternae, (3) typical pattern of the rough-surfaced endoplasmic reticulum, and (4) close contacts of astroglial processes with the somal surface. The most prominent features in the bullfrog spinal cord can be summarized as follows: the microneurons occupy the dorsal region as well as the region around the central canal of the gray, and the most dorsal part of the gray in exclusively occupied by these microneurons. They show, furthermore, a tendency to separate grossly into medial and lateral groups. No microneurons are visible in the ventral horn. According to the results obtained from the cytoarchitectonic comparison of the bullfrog spinal cord and the rat spinal cord, it can be said that in the former no differentiated laminar structures can be recognized, while in the latter the gray matter is sufficiently differentiated to permit full percellation.


Relative refractory state for late cutaneous allergic responses. The late cutaneous allergic response (LCAR) is a usual sequel to the wheal-and-flare (early) response in sufficiently intense cutaneous allergic reactions. Allergic reactions with early and late components were produced in the skin of the forearm by the intracutaneous injection of anti-IgE or allergen. One week later, these sites, which were normal in gross appearance, and separate control sites on the opposite forearm, were injected. At the sites of repeat reactions, the wheal diameter of the early response was the same but the LCAR was considerably smaller than at simultaneously injected control sites. This local relative refractory state for LCAR is immunologically nonspecific in the sense that it was manifest even when the antigen injected the second time had no evident immunologic relationship with the antigen injected initially. The refractory state for LCAR was present at 2 wk after the initial reaction, but it was no longer demonstrable after 3 wk. This local relative refractory state for LCAR may represent an inhibitory control mechanism for allergic reactions in man.


Human B lymphocytes in giemsa stained preparations. A mixed antiglobulin procedure has been developed to provide simultaneous study of cell surface immunoglobulin and detailed cytological features in Giemsa stained preparations. The percentage of surface immunoglobulin bearing lymphocytes, monocytes and granulocytes changed dramatically when lymphocytes were incubated at 37 degrees C, or following sheep erythrocyte rosette enrichment procedures.


The identification of human T and B lymphocytes by electron microscopy. Lymphocytes of peripheral blood, bone marrow, spleen, vermiform appendix, tonsil and Mantoux skin reaction were examined by electron microscopy (EM) and classified as T, B and Null cells by E-rosette and immunoglobulin membrane-receptor characteristics. The low pH and ionic strength of the fixative solution for EM, and some other minor procedural modifications, made it possible to distinguish B and T lymphocytes morphologically. T-cells have electron-dense cytoplasm and euchromatin in the nucleus whereas B-cells constantly have electron-lucent cytoplasm and euchromatin in the nucleus. A proportion of lymphocytes were unclassifiable by their ultrastructural features. These unclassifiable cells may be Null cells as determined by the classical techniques. The specificity and simplicity of this EM technique for T and B lymphocytes is especially useful for studies of immunocompetent-cell topography and cell-to-cell interaction in lymphoid organs. It may also be utilized for diagnostic purposes in immunocytic dyscrasias.


Comparative studies of humoral factors stimulating granulopoiesis in agar in vitro and in diffusion chambers. The factor stimulating granulopoiesis in diffusion chambers (DCF) was compared with the CSA in post-EMS in two ways: (1) Mouse bone marrow cells were maintained in suspension cultures, containing DCF or EMS, which were assayed at intervals for colony-forming cells, both in agar in vitro and in diffusion chambers. (2) The enhanced growth seen in chambers incubated in pretreated mice was compared with the CSA of serum and DCF recovered from these animals. The results show that the cells forming granulocytic colonies in agar in vitro and in diffusion chambers are closely related, if not identical, and that different sources of CSA may differ in their ability to maintain precursor cell numbers in suspension culture. The CSA of DCF did not correlate with growth enhancement in diffusion chambers or with the levels of CSA in the serum.


A conversion code from the RCGP to the ICHPPC classification system. Faculty members from four family medicine training programs participated in the production of a definitive conversion of the Royal College of General Practitioners Classification of Diseases as modified for use with problem-oriented medical records (RCGP) to the International Classification of Health Problems for Primary Care (ICHPPC). The method used to produce the conversion and the several problems encountered are described. A detailed translation with the appropriate ICHPPC equivalent for each RCGP diagnostic title and code number is provided.


Aqueduct stenosis. Case review and discussion. Twenty-seven cases of hydrocephalus associated with aqueduct stenosis are reviewed, and a further nine cases discussed in which hydrocephalus was present and the aqueduct was stenosed but some additional feature was present. This was either a meningocoele or an encephalocoele, or else the aqueduct was not completely obstructed radiologically at the initial examination. The ratio of the peripheral measurement from the inion to the nasion to the distance between the inion and the posterior lip of the foramen magnum is presented for each case with an outline of the ventricles. The cases behave as would be expected if the aqueduct was being blocked by the lateral compression of the mid-brain between the enlarged lateral ventricles. On reviewing these cases and other evidence it is suggested that non-tumourous aqueduct stenosis is more likely to be the result of hydrocephalus than the initial cause. The response to treatment is reviewed and a high relapse rate noted. It is suggested that assessment of the extracerebral pathways may be advisable before undertaking third ventriculostomy or ventriculo-cisternostomy.


A comparison of the energy balance in two successive isometric tetani of frog muscle. 1. Measurements were made of the energy produced as heat and work (h + w) and the chemical changes which occurred between the beginning and end of each of two periods of stimulation. The muscles contracted tetanically under isometric conditions. Each period of stimulation (tetanus) lasted 5 sec and there was an interval of 3 sec between them. The tension developed in the second tetanus was 91% of that in the first.2. The observed (h + w) was greater in each tetanus than the quantity expected from the measured chemical changes. This excess was 230 +/- 43 mJ/g dry wt. (mean +/- S.E. of mean) in the first tetanus, but only 89 +/- 46 mJ/g in the second tetanus (mean +/- S.E. of mean). The result for the first tetanus agrees with previous findings.3. The observed (h + w) was divided into two parts, labile and stable, which were defined by Aubert (1956). This division was made on the basis of the time course of the (h + w) production, without reference to the chemical changes. The labile part of the (h + w) has an exponentially declining rate, and the stable part has a constant rate.4. The observed (h + w) was less in the second tetanus than in the first. This was due largely to the decrease in the labile part in the second tetanus; it was only ca. 0.35 of that in the first tetanus. However, the stable part remained relatively constant, 0.83 of that in the first tetanus. Aubert & Maréchal (1963) and Aubert (1968) have reported similar results.5. Having divided the (h + w) into the stable and labile parts, we found that the stable part could be accounted for by the chemical change, but the labile part could not. Thus, for both tetani, the stable part of the energy is about equal to the explained energy, and the labile part is about equal to the unexplained energy. The possible interpretations of these equalities are discussed.


Action potentials in slow muscle fibres of the frog during regeneration of motor nerves. 1. Pyriformis muscles of Rana temporaria were denervated by crushing the sciatic nerve inside the pelvis. At different times during regeneration of the nerve, slow muscle fibres were examined for the presence of all-or-none responses. 2. During the early period of re-innervation (35-60 days), slow muscle fibres were found to be non-selectively re-innervated by (foreign) fast-conducting motor axons. All slow fibres during this period were able to produce full sized action potentials, with overshoot. 3. Action potentials markedly decreased in amplitude and eventually disappeared completely between day 61-110 following denervation; during this period, slow muscle fibres were re-innervated by slowly-conducting motor axons. 4. Functional re-innervation by slowly-conducting motor axons, in the late stages of re-innervation, was not a necessary condition for the suppression of the action potential. Slow fibres innervated by fast motor axons, as well as denervated slow fibres, lost the action potential simultaneously with slow fibres which were re-innervated by slowly-conducting motor axons. 5. It is suggested that (small) slowly-conducting motor axons can exert a 'trophic' influence on the slow fibre membrane, independent of their synaptic function.


Metabolism of the frog outer segments: a kinetic study. 1. The reaction of the high-energy phosphate esters of the frog isolated rods, with the firefly lantern extract, has been studied by recording the luminescence in a stopped-flow apparatus. The onset of the reaction was determined by the rapid mixing of the firefly lantern extract with the high-energy phosphates released from the rods fragmented during the mixing.2. The time course of the reaction, i.e. of the luminescence, was not typical of adenosine-5'-triphosphate (ATP), indicating that the major part of the rod nucleotides is not ATP.3. The isolated rods were fragmented 1 sec-2 min after a flash of light. As soon as 1 sec after illumination, a substantial decrease of the luminescent yield has been detected in a range of light bleaching from 0.007 to 20% of the rhodopsin, indicating an early reduction of the high-energy phosphate esters.4. At longer times, flashes that bleached 7 or 20% of the rhodopsin induced a progressive decrease of the luminescent yield that was half completed in 6-9 sec, and was nearly complete in 20 sec, whereas a more or less complete recovery was observed after flashes bleaching from 0.7 to 0.007% of the rhodopsin, indicating the presence of buffering mechanisms.5. Also, the time course of the reaction was modified in a complex way after stimulation of the rods, suggesting that other nucleotides beside ATP are hydrolysed.6. The light-induced reduction of the high-energy phosphates has been observed also in broken rods, in the presence of the calcium chelating agent EGTA, suggesting that calcium is not needed for this effect.7. Cyclic guanosine monophosphate (10(-4)M) interfered with the photic effect.8. The rapid effect of light on the content of high-energy phosphate esters suggests a physiological role in the mechanism of excitation.


Location of U.V.-absorbing substance in isolated skeletal muscle fibres. The effect of stimulation. 1. In an attempt to study the intracellular location of ATP in skeletal muscle the distribution of substances which absorb light at 260 nm wave-length has been studied in isolated muscle fibres with the aid of a modified U.V.-microscope.2. U.V.-absorption in resting frog fibres was found to be higher in the I band than in the A band which confirms earlier findings. In stretched fibres (sarcomere length 2.9-3.6 mum) an absorbing substance could be seen to be concentrated in a pair of narrow lines, centred at the Z-line. The separation of the lines increased with increasing sarcomere length.3. Snake fibres, with sparse triads located at the A-I junction, displayed an absorption pattern very similar to that of frog fibres. It is concluded that it is unlikely that the absorbing substance is associated with the sarcotubular system.4. The absorption pattern of frog fibres remained unchanged during a tetanus. No clear changes could be detected after a period of stimulation, neither after single twitches nor after repeated tetani.5. In further attempts to cause exhaustion, metabolically poisoned fibres were stimulated repetitively until they went into rigor. The absorption pattern was essentially unchanged also when rigor tension started to develop.6. The characteristic absorption pattern was observed also in glycerol-extracted fibres. It was confirmed by spectrophotometry that glycerol-extraction led to the disappearance of a large amount of a substance with the spectral characteristics of ATP.7. The higher U.V.-absorption in the I band does not prove that the major part of the ATP in the fibre is concentrated here; the absorption could either be due to a minor fraction of the ATP or to RNA.


Ultraviolet-induced alterations of the sodium inactivation in myelinated nerve fibres. Ultraviolet radiation irreversibly reduces the sodium permeability in nerve membranes and, in addition, induces a change of the potential dependence of the kinetic parameters of sodium inactivation in the node of Ranvier. This second ultraviolet effect shifts the kinetic parameters of sodium inactivation h infinity (V), alpha h (V), and beta h (V) to more negative potentials (no changes of the slopes of the curves). The amount of the displacement delta V along the potential axis is equal for the three parameters and depends on the ultraviolet dose. It is about delta V = --10 mV after an irradiation dose of 0.7 Ws/cm2 at 280 nm. Both ultraviolet-induced effects depend on membrane potential and on the wavelength of the applied radiation. But while the potential shift is enhanced at more negative holding potentials, the ultraviolet blocking is diminished and vice versa. Further, the ultraviolet-induced potential shift is greater at 260 nm than at 280 nm, whereas a maximum sensitivity of ultraviolet blocking is found at 280 nm. Therefore, the two radiation effects are the result of two separate photoreactions. For explanation of the radiation-induced potential shift it is assumed that ultraviolet radiation decreases the density of negative charges at the inner surface of the nodal membrane. From this hypothesis a value for the inner surface potential psii was derived. --19 mV less than or equal to psii less than or equal to --14 mV.


Passive ionic properties of frog retinal pigment epithelium. The isolated pigment epithelium and choroid of frog was mounted in a chamber so that the apical surfaces of the epithelial cells and the choroid were exposed to separate solutions. The apical membrane of these cells was penetrated with microelectrodes and the mean apical membrane potential was --88 mV. The basal membrane potential was depolarized by the amount of the transepithelial potential (8--20 mV). Changes in apical and basal cell membrane voltage were produced by changing ion concentrations on one or both sides of the tissue. Although these voltage changes were altered by shunting and changes in membrane resistance, it was possible to estimate apical and basal cell membrane and shunt resistance, and the relative ionic conductance Ti of each membrane. For the apical membrane: TK approximately equal to 0.52, THCO3 approximately equal to 0.39 and TNa approximately equal to 0.05, and its specific resistance was estimated to be 6000--7000 omega cm2. For the basal membrane: TK approximately equal to 0.90 and its specific resistance was estimated to be 400--1200 omega cm2. From the basal potassium voltage responses the intracellular potassium concentration was estimated at 110 mM. The shunt resistance consisted of two pathways: a paracellular one, due to the junctional complexes and another, around the edge of the tissue, due to the imperfect nature of the mechanical seal. In well-sealed tissues, the specific resistance of the shunt was about ten times the apical plus basal membrane specific resistances. This epithelium, therefore, should be considered "tight". The shunt pathway did not distinguish between anions (HCO--3, Cl--, methylsulfate, isethionate) but did distinguish between Na+ and K+.


L-asparagine requirements of human T-lymphocytes and B-lymphocytes in culture. The characterization of two human T-lymphocyte lines revealed that they required exogenous L-asparagine for cell growth, whereas all four B-cell lines studied were L-asparagine independent. T-cells were 800-2,000 times more sensitive to Escherichia coli L-asparaginase than were B-cells. The cytotoxic effects of a high concentration of L-asparaginase on B-cells were not related to the hydrolysis of L-asparagine but were due to heat-labile and heat-resistant substances in the enzyme. The findings were consistent with reports that L-asparaginase is effective in suppressing cellular immunity and inducing remission in patients with acute lymphocytic leukemia, mainly a non-B-cell disease. Thus these cell lines provide in vitro models for the study of a nutritional approach to chemotherapy or immunotherapy.


Species and rat strain variation in pancreatic nodule induction by azaserine. Subtoxic doses of azaserine induced atypical acinar cell nodules (AACN) in the pancreases of outbred Wistar rats, inbred W/LEW and F344 rats, and outbred Charles River CD-1 albino mice 4-6 months after initiation of treatment in the growing animal. These AACN apparently represented preneoplastic lesions, some of which have the potential to develop into adenomas or adenocarcinomas. Wistar and W/LEW rats were highly responsive to nodule induction; AACN developed in about 90% of the outbred Wistar rats and in all of the W/LEW rats tested. F344 rats were less susceptible and developed about 10% as many AACN as the Wistar rats. Female rats developed approximately half as many AACN as males. The mouse was intermediate in response between the F344 and the two Wistar rats. Syrian golden hamsters and strain 13 guinea pigs were relatively unresponsive. These studies of azaserine-induced AACN provided a basis for selection of carcinogenic azaserine regimens and suggested that the young male W/LEW rat was the most sensitive of the animals studied.


Growth of human melanoma in nude mice: suppression by T-lymphocytes from the tumor donor: brief communication. Human malignant melanoma cell lines established in tissue culture were successfully transplanted sc into BALB/c nude mice. The growth rate of the resulting tumors was significantly suppressed when lymphocytes from the patient in whom the tumor arose were injected iv into BALB/c nude mice at the same time as sc tumor transplantation, but inoculation with lymphocytes from a person without a tumor was ineffective. Cell separation identified T-lymphocytes as the active subpopulation. Growth of the tumors was also significantly suppressed by reconstitution of the mice with normal BALB/c lymphocytes; lymphocytes from BALB/c mice previously immunized against the melanoma line were not more effective than nonimmune lymphocytes in preventing tumor growth. Sera from normal BALB/c mice or BALB/c mice immunized against a human melanoma cell line effectively suppressed growth of that cell line in BALB/c nude mice if given at the time of tumor transplant. The results suggested that, whereas murine lymphocytes reconstitute the ability of nude mice to react to xenogeneic antigens on the human tumor, human lymphocytes showed greater specificity to autologous human melanoma-associated antigens.


Deficient mitogen-induced virus plaque-forming cells in patients with localized cancer. The virus plaque assay (VPA), an assay capable of enumerating mitogen- or antigen-sensitive T-lymphocytes in a given cell population, was applied to the study of mitogen responses of peripheral blood leukocytes (PBL) in 50 patients with localized, solid cancers and in 29 normal controls. Concanavalin A (Con A)-responsive virus plaque-forming cells (V-PFC) were significantly reduced in the patients as compared with those of the controls. PBL from 20 of the patients but only 2 of the controls failed to show significant increments in V-PFC over background when cultured in the presence of Con A. This deficient response was also present in the patients when phytohemagglutinin was used as the mitogenic agent. Mitogen-stimulated uptake of [3H]thymidine (TdR) in parallel cultures failed to show a statistically significant difference between the patients and the controls, though some patients showed diminished stimulation in this assay. The VPA thus appeared to detect a defect of T-lymphocyte function not found in the [3H]TdR incorporation assay.


Natural cell-mediated immunity to lymphoma cells. I. Characteristics of effector cells in a cytostasis assay in vitro. Spleen cells from normal, nonimmune, CBA or (CBA X AKR)F1 mice markedly and rapidly inhibited the incorporation of [3H]thymidine by two different T-cell lymphomas in an in vitro cytostasis assay. These were the I-529 lymphoma of spontaneous AKR origin and the Moloney murine leukemia virus-induced YAC lymphoma of A mouse origin. Spleen cells were the most efficient inhibitors for both types of target cells, whereas lymph node cells were much less active and thymus cells showed little or no activity. Granulocytes, as well as conventional T- and B-lymphocytes, were excluded as important contributors to the cytostatic cell population. Spleen cells were separated on nylon wool, Sephadex G-10 columns, or plastic petri dishes and tested for activity in the cytostasis assay or for cytotoxicity against 51Cr-labeled lymphoma target cells. Adherent cells carried almost all cytostatic activity against the AKR lymphoma but also showed significant cytotoxic activity against these target cells. In addition, the cytostatic activity against the YAC lymphoma was mainly due to adherent spleen cells, but nonadherent cells were relatively more active against this target than against I-529 cells. Such nonadherent spleen cells further showed increased cytotoxic activity, compared to the whole spleen cell population.


["Transfer factor" in ophthalmology (author's transl)]. After considering general preliminary immunological aspects, the author discuss the "transfer factor" of Lawrence (TF) which is one of the lymphokines that are produced by the thymus-dependent lymphocytes (LT). This factor whose nature and the probable constituent fractions are also considered, is the initiator of the cellular immunity. In immunodeficiencies, the LT should be stimulated by introducing the TF in the organism (immunotherapy). The possible use of other immunostimulating substances, which could replace the TF (levamisole BCG, thymosine), is also presented. Finally the author emphasize the large perspectives in the use of these factors in Ophthalmology: herpes, uveitis, melanoma, primary retinitis pigmentosa etc.).


The germfree leopard frog (Rana pipiens): preliminary report. Eggs and sperm were aseptically collected from leopard frogs (Rana pipiens) and passed into sterilized flexible film isolators. Egg fertilization was accomplished, and germfree tadpoles were produced. The germfree tadpoles were active and free-swimming for 3 weeks, but only 6.2% survived to 4 weeks of age. None survived after the 4th week.


Immunoprofile studies for patients with bronchogenic carcinoma. I. Correlation of pretherapy studies with survival. The general immune competence of 146 patients with bronchogenic carcinoma was measured, prior to irradiation therapy, by determining dinitrochlorobenzene (DNCB) reactivity, delayed cutaneous hypersensitivity (DCH) response to microbial antigens, peripheral lymphocyte counts, peripheral T and B lymphocyte counts, and the response of patient's lymphocytes to stimulation by phytohemagglutinin (PHA), concanavallin A (Con A) and pokeweed mitogen (PWM). Analyses were performed by the life-table method to determine the correlation of the immune status of these patients with survival rates. Statistically significant differences in survival were noted between the groups of patients with normal values when compared with the patients with abnormal values for the majority of the tests of general immunity. A stage of disease correlation with survival rate was noted for all groups of patients with abnormal immune measurements, but it was absent for many of the immune parameters when patients with normal values were compared. The effects of histology, age, and sex did not appear to influence the survival data as significantly as did the immune status of the patient. These data indicate that measurements of general immune competence may be of significant prognostic value for the management of patients with bronchogenic carcinoma. The measurement of DNCB reactivity shows the strongest correlation with survival rate.


[State of vestibulotonic reflexes of rat hindlimb muscles after space flight on the satellite 'Cosmos-605"]. The state of the vestibulo-tonic reflexes on hind-limb muscles of rats after the Cosmos-605 flight was investigated. As compared with the controls the flight animals showed a significant decrease of spontaneous bioelectric activity of muscles-extensors of hind-limbs. The response to an adequate stimulation of the vestibular organ was noticeably increased. The postflight changes were functional, varied in a wave-like pattern and decreased gradually.


Disappearance of electrocardiographic pattern of inferior wall myocardial infarction after aorta-coronary bypass surgery. Three cases are presented showing the disappearance of electrocardiographic (ECG) evidence of old inferior wall myocardial infarction (MI) after aorta-coronary bypass surgery. Evidence is presented to suggest that the loss of Q waves may be the result of reperfusion of the ischemic myocardium (two cases) and the "cancelling effect" of a new perioperative myocardial damage upon the ECG evidence of an old myocardial infarction (one case). Q waves do not always indicate permanent myocardial scar formation; they are sometimes transient and reversible. Review of the literature provides further experimental and clinical evidences to suggest that surgical reperfusion of peri-infarction ischemic myocardium is an explanation for the ECG change. Pre- and postoperative angiographic and ventriculographic correlations are needed to further clarify the mechanism and clinical significance of such cases.


Normal opaque cerebellopontine cisternogram. An attempt has been made through this study to establish a tumor suspect pool of 100 patients, each one highly suspect because of a single or usually several strong clinical indicators of a retrocochlear lesion. In turn each patient has been proven tumor negative by virtue of a normal opaque cerebellopontine cisternogram. This has given us a unique opportunity to critically reassess the clinical indications of VIIIth nerve tumor from a reverse or negative viewpoint. All data from these patients has been carefully analyzed in relation to indication for opaque cisternography, clinical symptomatology, vestibular function, final etiologic diagnosis, and the associated special auditory tests, tomograph of the internal auditory canal, the associated vestibular aqueduct findings. This paper parallels our earlier study of 121 surgically proven schwannomas providing a total tumor suspect pool of 221 patients with a comparable tumor positive-tumor negative distribution.


[Fatal poison disease of a child following massive wasp stings (author's transl)[]. A child aged 4 years was stung by more than 250 wasps. There was no anaphylactic shock. There rather were increasingly heavy ictero-hemorrhagic symptoms with simultaneous insufficient kidney function. On the second day of the disease disorders of the CNS started, as well as circulation insufficiency and disorder of the heart function. According to the signs there was no intravasal coagulation or hemolysis. Heavy doses of corticoids were successless, just as a peritoneal dialysis starting on the 3rd day of the disease. The child died 5 and 1/2 day after the wasps' attack. The pathophysiology and the possible therapeutic consequences of the case as well as rapid protective actions in such a case of insect attack are being discussed.


Sulfite oxidase deficiency. Biochemical and clinical investigations of a hereditary metabolic disorder in sulfur metabolism. Study of a 4 1/2-year-old boy with the unusual combination of acute infantile hemiplegia, ectopia lentis and the absence of homocystinuria showed large amounts of abnormal sulfur-containing metabolites (sulfite, thiosulfate and S-sulfocysteine) in the urine. Sulfite and S-sulfocysteine were also present in the plasma. His inorganic sulfate excretion was only 50 per cent of total sulfur, as compared with 75 to 95 per cent by controls. Loading with L-cysteine hydrochloride and L-methionine further increased the excretion of sulfite and thiosulfate, but not inorganic sulfate excretion. Sulfite oxidase activity in skin fibroblasts average 1.07 nmol of cytochrome d reduced per milligram of protein per minute in control lines; it was not detectable (less than 5 per cent) in the patient. Activity was reduced in both parents (0.50 in the father and 0.32 in the mother)--compatible with autosomal recessive inheritance. Good biochemical responses to a low sulfur amino acid diet suggest that early treatment may benefit the patient.


Cultured epithelial cells of cornea, conjunctiva and skin: absence of marked intrinsic divergence of their differentiated states. Keratinocytes of three different epithelia grown in cell culture express a large number of differentiation markers with either no differences or relatively small differences, depending on the species. Much of the distinctive phenotype of these epithelia in vivo must be due to external modulation and relatively little, at least in the case of the human, to permanent intrinsic divergence during development.


[Effect of calcium channel blockaders (verapamil, D-600 and manganese ions) on mediator release from frog muscle motor nerve endings]. The reduction in the EPPs quantum content produced by manganese ions (0.4-5.0 mM) was observed in the frog sartorius muscle. In contrast to the inhibitory action on the evoked release, manganese ions increased a spontaneous transmitter release. Verapamil (1-10(-6)-5-10(-5) g/ml) and D-600 (2.5-10(-5) g/ml) did not inhibit the evoked release but increased the spontaneous one. All the calcium antagonists studied were able to prevent the facilitatory effect of imidazole (3 mM) on neuromuscular transmission. Verapamil (5-10(-6)-5-10(-5) g/ml) disturbed the action potential generation during the repetitive stimulation of the motor nerve. Manganese ions were ineffective in this respect. A conclusion is made that the calcium ionic channels in the nerve terminals differ from the calcium channels in some other tissues (heart, soma of neurons etc.).


[Relationship between temperature and calcium ion concentration in the medium and the effect of imidazole, guanidine and theophylline on mediator release at the frog neuromuscular synapse]. The effect of imidazole, guanidine and theophylline on the spontaneous (frequency of miniature end-plate potentials) and evoked (quantum content of end-plate potentials) release of transmitter was studied in the experiments on isolated frog neuromuscular preparation under different temperature and calcium concentration. All the drugs studied were able to enhance the quantal content and frequency under 20 degrees C and 0.5 mM Ca2+. The potency of drugs for increasing evoked release could be ranked as follows: imidazole approximately guanidine greater than theophylline, but for increasing spontaneous release; theophylline greater than imidazole approximately guanidine. Only the effect of theophylline on the frequency depended on temperature. Imidazole and theophylline were independent on calcium concentrations. The possible differences in the mechanism of drug action on spontaneous and evoked release of transmitter are discussed.


[Spatial deployments of morphogenetic movements as elements of the oral field in anuran amphibians. I. Structurally stable morphogenetic movements]. The movements of cells in the oral field of anuran embryos were followed by means of orto- and heterotopic transplantations of the ectoderm fragments. To mark individual ectoderm regions, the embryos were used which differed from each other by colour. The cells polarize along the apical-basal layer axis and the polarization spreads along the layer as a waver embracing consecutively new and new cells. The waves of morphogenetic rearrangements from the spatial deploiments of morphogenetic movement, i. e. the transition between the local morphologies of the layer which replace one another in time is swept continuously in space. The presence of spatial sweep is the necessary condition for the structural stability of morphogenetic movements.


[Spatial deployments of morphogenetic movements as elements of the oral field in anuran amphibians. II. The structure of the oral field]. The structure of morphogenetic movements in the oral field of Anura was studied. The movement of any region of the oral field depends on several "elementary waves" of morphogenetic rearrangements, each of them being swept in space along the same cell layer. The waves of morphological rearrangements of cells from different layers are coupled with each other in a stable manner. The cells of the given layer are involved in their morphogenetic movements consecutively, whereas the morphogenetic movements of cells in the interrelated layers are developed in parallel. The waves of morphological rearrangements are those of contact polarization of the cells and, under certain conditions, are spread within several minutes.


Thrombocythemia as a cause of oral hemorrhage. Thrombocythemia is characterized by an increase in platelet numbers coupled with abnormal function. Three cases diagnosed after referral to an oral surgeon are presented. In each case the reason for referral concerned excessive dental hemorrhage. Thrombocythemia should be included in the differential diagnosis in cases of oral hemorrhage.


Psychophysical determination of the phase characteristic of the vestibular system of man for sinusoidal oscillation in yaw. The phase characteristic of the vestibular system of man was determined for sinusoidal oscillation in yaw in the frequency range from 0.0025 to 0.4 Hz. Three different sets of experimental conditions were used: (1) a dark room with a fixation light; stimulus: sinusoidal rotation; (2) a dark room without a fixation light; stimulus: sinusoidal rotation + noise, and (3) a dark room without a fixation light; stimulus; sinusoidal rotation. the sensation leads the velocity by about 90 degrees at 0.005 Hz. The phase lead decreased for higher frequencies becoming nearly zero at 0.05 Hz and remaining constant in the frequency range 0.05 to 0.4 Hz. A phase lag was not found. At very low frequencies (less than 0.005 Hz), the phase lead was more than 90 degrees. The results can be described in terms of a second-order model with time constants Tau1 = 20 sec and Tau2 = 0.013 sec and an adaptation term with a time constant of Taau = 0.40 sec.


[The Ly-Li system, a new locus of the HLA complex]. Antibodies raised through immunization of volunteers not differing for serologically defined HLA-A, B and C antigens enabled us to define since 1975 a new antigenic system controlled by the HLA complex. These new allo-antigens, designated Ly-Li, are expressed on B lymphocytes but are absent from T lymphocytes, platelets, erythrocytes and fibroblasts. Multiple alleles belong to the Ly-Li differentiation antigen system. The gene frequencies of three alleles thus far detected are 0.1558 for Li2; 0.1867 for Li3 and 0.122 for Li4. Like in the serologically defined HLA antigen systems, "inclusions" were observed also in Ly-Li system, suggesting the existence of private and public specificities. Among 48 families, 23 were informative in showing that the Ly-Li locus segregated with the HLA complex. Data on three families with recombinant haplotypes between HLA-B and D, and between Bf and HLA-D, indicated that the Ly-Li locus was near HLA-D (possibly identical with HLA-D). Anti-Ly-Li antibodies inhibited cellular proliferation in mixed leucocyte culture (MLC) primarily when directed against the antigens of stimulator cells. There was a good correlation between Ly-Li and HLA-D alleles, particularly between Li2 and DW5 (r = 0.70). Usually, HLA-D specificities were "included" in the related Ly-Li specificities, but not vice-versa. In contrast, there was a higher correlation between Ly-Li specificities and those detected by the PLT (primed lymphocyte test). The Ly-Li system seems to be of great importance for the functional characterization of lymphocyte subpopulations, for the selection of the best donor in organ transplantation, and for the investigation of susceptibility genes in diseases associated with HLA-D.


[Immunological tests in the diagnosis and prognosis of disseminated lupus erythematosus, before treatment (author's transl)]. Sixty-four patients classified according to clinical manifestations, and renal pathological lesions have been submitted to a detailed immunological study before treatment. Four tests have provided significant correlations: antinative DNA antibodies (studied by a Farr test), C3, E rosette and cryoglobulins. The simultaneous considerations of these 4 parameters is however necessary in a given patient because each of them, taken separately, has no absolute value and may sometimes be clearly abnormal in patients with apparently benign outcome.


Sequential stages of human T lymphocyte differentiation. Induction of thymus-dependent lymphocyte (T cell) differentiation was performed in vitro with thymic factors as inducers. T cell precursors from human bone marrow first expressed surface differentiation antigens and then acquired the capacity to form rosettes with sheep erythrocytes. The latter marker could not be induced when cells with differentiation antigens had been eliminated. The proliferative responses to phytomitogens or to allogeneic stimuli appeared to be characteristics of later stages in differentiation that also can be induced or amplified by in vitro incubation of marrow cells or thymocytes with thymic factors. When phytomitogen-responsive cells from peripheral blood were inactivated in vitro, the allogeneic response was enhanced. Although these responses are acquired almost concomitantly, they are therefore envisioned to be characteristics of separate T cell subsets. After immunological reconstitution of patients, the T cell development in vivo involves a succession of differentiation events similar to that described above. Our experiments with mice, using similar methods, have also shown that graft-versus-host inducing capacity is a function of a cell population distinct from that which yields a proliferative response to in vitro stimulation by phytohemagglutinin. These results support our model of sequential differentiation of human prothymocytes into various subsets of mature T cells.


HLA-D associated alloantisera react with molecules similar to Ia antigens. Two human alloantisera specific to bone marrow-derived lymphocytes (B cells) were shown to precipitate polypeptide chains of 29,000 and 34,000 daltons from human lymphoblastoid B cell lines. These molecules are similar to murine Ia antigens and are also precipitated by a rabbit B-cell specific heteroantiserum. Since the alloantisera are thought to recognize determinants coded by HLA-D or closely linked loci, these data support the hypothesis that these B-cell specific alloantigens are the human counterpart of the mouse Ia antigens and may be the products of HLA-D.


Variants of 3T3 cells lacking mitogenic response to epidermal growth factor. We have previously demonstrated that epidermal growth factor (EGF) can serve as a potent mitogen for 3T3 cells. We have now selected variant 3T3 cell lines unable to respond to EGF, in order to define cellular events unique to the EGF response and to distinguish which of these events are necessary and which are merely correlative to mitogenesis. By simultaneously treating cells with EGF and colchicine, we eliminated those cells stimulated by EGF to enter mitosis. Of the eight clonal EGF nonresponder variants selected by this procedure, none retains a functional EGF receptor. The EGF nonresponsive va-riant lines still retain the ability to respond to other mitogens.


beta-Endorphin: development of tolerance and its reversal by 5-hydroxytryptophan in cats. Tolerance to beta-endorphin developed acutely in cats if the administration of the peptide was repeated within the first 24 hr. The tolerance was reversed immediately by systemic administration of the serotonin precursor, 5-hydroxytryptophan. It was further shown that 5-hydroxytryptophan potentiates the analgesic effect of the subliminal dose of beta-endorphin.


Transport of alpha-amylase across the basolateral membrane of the pancreatic acinar cell. The flux of alpha-amylase (1,4-alpha-D-glucan glucanohydrolase; EC 3.2.1.1) across the basolateral membrane of the acinar cell was measured in the cell-to-bath direction using the whole rabbit pancreas in organ culture. This in vitro preparation is polarized so that apical and basolateral secretions can be collected separately. The unstimulated amylase flux from cell to bath was substantial at the initial rate (approximately three times the concurrent apical flux). With time, bath amylase approached a steady-state concentration, suggesting an equilbrating process. During the same time interval, ductal amylase secretion remained constant. At the steady state, the amylase concentration in the bath was at least an order of magnitude less than its ductal concentration. Hourly replacement of bathing medium reproduced the initial rate of amylase release into the bath for five consecutive hours. Pancreozymin (cholecystokinin), a peptide hormone, did not alter the steady-state bath amylase content, although it greatly augmented ductal amylase secretion. In contrast, a cholinergic agonist greatly increased both the flux from the cell to bath and the ductal secretion of amylase. Taken together, these results indicate a natural bidirectional permeability of the basolateral membrane to digestive enzyme and support evidence previously obtained suggesting that such a permeability might exist.


Periventricular spread of tumor demonstrated by computed tomography. Spread of intracranial neoplasms through the periventricular tissues of the brain is well known to neuropathologists, but is almost never recognized by the usual neuroradiologic techniques of angiography and pneumoencephalography. Periventricular tumor spread can, however, be readily dmonstrated by contrast-enhanced CT scanning. This report documents 4 cases of periventricular tumor diagnosed by CT scanning.


Hypoimmunoglobulinaemia and aplastic anaemia. Serum immunoglobulin levels were estimated in 19 patients with aplastic anaemia. Although the mean levels for IgG, IgA and IgM for the group as a whole were within the normal range, 8 individual cases showed low levels of one or more immunoglobulin class, suggesting a disturbance in immunoglobulin production. One of these patients had a thymoma, and another positive tests for anti-nuclear factor, but there was no evidence of auto-immune disease in the others. It is suggested that 'aplastic anaemia' may sometimes be a disease due to injury of a stem cell subserving both haemopoietic and immunological function.


Functional heterogeneity of splenic T lymphocyte subpopulations. I. Determination of splenic subpopulations by the use of mitogneic probes. The results reported here suggest that there exist two T-cell-mitogenic responsive populations in the spleen--one that is responsive to concanavalin A (Con A) and a second one that is responsive to Con A and phytohemagglutinin (PHA). Using an in vitro restimulation system, we have found that a primary in vivo activation with Con A effectively suppresses the subsequent restimulation response to PHA. However, in the reverse experiment, a primary in vivo PHA activation had little effect on the ability of cells to be restimulated with Con A. The suppression seen was due to a refractory recovery period displayed by all cells after previous activation and not to a nonspecific steric hindrance of mitogenic activation receptors due to the lectin remaining on the cell surfaces.


HLA-D-associated 'Ia-like' antigens on human macrophages. Human macrophages procured by culture of adherent peripheral blood mononuclear cells were investigated for reactivity in complement-dependent cytotoxicity tests with antisera having specificity for HLA-D-associated 'Ia-like' B-cell antigens. The antisera were found to be cytotoxic for 30%-70% of the macrophages from donors whose B cells were also reactive, and absorption with B cells also removed macrophage cytotoxicity. A B-cell xenoantiserum was also cytotoxic to macrophages. It is concluded that the HLA-D-associated 'Ia-like' antigens present on B cells are also expressed by macrophages, at least on a subpopulation.


T-lymphocyte recognition of alloantigen in vitro. I. Significance of Fc-receptor-positive T and B stimulator cell in the generation of cytotoxic T lymphocytes. The present report deals with our attempts to characterize the potent stimulator cell(s) that induce Fc receptor (FcR)-negative T lymphocytes to differentiate into cytotoxic T lymphocytes in vitro. We found two categories of such cells: [1] resting B cells, FcR+ T cells, and macrophages and [2] T cells either activated in 800-R-irradiated mice against H-2 antigens or M-locus antigens or activated in vitro by concanavalin A. The distinction between potent and weak stimulator cells is discussed in relation to the surface antigenic markers and the immunological function of these cells.


Changes in age and need for care among patients in a geriatric institution during a two-year period. Two cross-sectional studies, carried out at an interval of exactly 2 years at a geriatric institution accomodating about 1400 residents, show an increase in the age of the patients and in the need for care after the 2 years. An analysis of the conditions shows that the changes are due to the surviving patients becoming older and in need of more care, without adequate compensation for this trend having been taken into account when admitting new patients. The admittance and staff aspects connected with these changes are discussed.


[Screening of newborn infants in cystic fibrosis. Evaluation of a 4-year study in Switzerland]. The results of an evaluation over 4 years (1973-1976) of 16,620 BM-tests (Boehringer-Mannheim newborn screening for cystic fibrosis) at 8 hospitals in Switzerland are presented and the data from analysis of albumin, protein and alpha1-antitrypsin concentrations, and on trypsin-inhibitory capacity of the meconia are discussed. 99.5% of the tests were negative. Of the remaining 0.5% BM-positive tests, the diagnosis of cystic fibrosis required confirmation by sweat test and clinical course in 6 cases, or 0.04% of the total collective. The test was false-negative in 2 cases (0.012%), of which one had a primary pulmonary form of cystic fibrosis. The study shows that the BM-test, as screening test for cystic fibrosis, makes it possible to distinguish between "normal" and "suspect". By calculating the ratio albumin to alpha1-antitrypsin, it would be possible to verify the probability of a reliable diagnosis as early as a few days after birth. As before, however, it would be indispensable to confirm the diagnosis of cystic fibrosis by a sweat test with pilocarpin iontophoresis. By consistent screening in all obstetric and pediatric clinics it would be possible to improve early diagnosis still further.


Arteriosclerosis: is stress-induced immune suppression a risk factor? Female Sprague-Dawley rats, purchased as retired breeders, developed arteriosclerosis that was accompanied by immune complex deposition in the arterial lesion and depressed immune responsiveness to T cell mitogens.


Simultaneous effects of erythropoietin and colony-stimulating factor on bone marrow cells. Erythropoietin or colony-stimulating factor, or both, were added to rat or mouse marrow cell cultures, and the responses to each inducer were measured. Colony-stimulating factor caused the suppression of erythropoietin-stimulated hemoglobin synthesis, and erythropoietin caused the suppression of the granulocyte-macrophage colony formation that is dependent on colony-stimulating factor. The extent of suppression by each inducer was dose-dependent. Marrow cells from plethoric rats were more sensitive to suppression of erythropoietin action by colony-stimulating factor than were normal marrow cells. These findings suggest that either (i) the receptors for erythropoietin and for colony-stimulating factor have overlapping specificities and that the "wrong" inducer may bind without having an inductive effect, or (ii) the target cells for erythropoietin and colony-stimulating factor are very closely related or are the same.


Gastric mucosal barrier, drug-induced acute erosive gastritis and stress ulcer. Gastric mucin probably plays an insignificant role in the protection of gastric mucosa. The metabolic integrity of the mucosal cells is important in the maintenance of the gastric mucosal barrier. Various drugs and "stress" break the gastric mucosal barrier, allowing increased back diffusion of hydrogen ions and causing gastric erosions, stress ulcers, and gastric bleeding. Presence of acid seems to be necessary for the occurrence of these lesions. Acute gastric mucosal lesions as a cause of upper gastrointestinal bleeding are best diagnosed by fiberoptic endoscopy. Antacids may be effective in preventing these lesions.


Central hemodynamics in acute gastrointestinal bleeding. In 15 patients with acute gastrointestinal bleeding, central hemodynamics were monitored by means of a flow directed thermodilution catheter. Also, the systemic blood pressure, heart rate, blood volume and oxygen saturation in arterial and mixed venous blood were measured. In patients without cardiac insufficiency, the pulmonary artery mean pressure was found to be the hemodynamic parameter giving the most clear and constant evidence of hypovolemia. In patients with left ventricular failure and hypovolemia, the pulmonary artery pressures revealed cardiac insufficiency, and the central venous pressure indicated the degree of hypovolemia. The method has proved useful in observing patients with acute gastrointestinal hemorrhage complicated by cardiac disease, cirrhosis of the liver or the frailty of old age.


The mechanisms of the action of electrical stimulation of muscles. The mechanisms of the action of electrical stimulation of muscles are discussed. We believe that the principal cause for the good results obtained in cases of stress incontinence with electrical stimulation must be due to the formation of a better reflex in contraction of the muscles of the pelvic floor. This, however, envolves changes at the level of the spinal cord. By the help of stimulation the patient learns to use the urethral sphincter and secondary forces of retention in a better and a more proper way. The good results obtained in the treatment of some cases of nocturnal enuresis by anal plugs require yet another explanation. It can be considered that in nocturnal enuresis the unconscious inhibition of the reflex mechanism for emptying the bladder is not developed enough. From the experience we know that vigorous voluntary activation of the muscles of the pelvic floor inhibits the contraction of the detrusor muscle. In this way it is possible to depress the urging sensation to urinate. In the paper we have tried to demonstrate this mechanism objectively. On the basis of our findings we believe that the good results in treating nocturnal enuresis may be due to this mechanism of stimulation.


Liver dysfunction in patients with hemophilia A, B, and von Willebrand's disease. Ninety-five patients with Hemophilia A, B and von Willebrand's disease followed over a three year period were evaluated for liver disease. Half of the patients were treated episodically and half received additional prophylactic treatment. Fifty-five per cent have significant transaminitis (elevated SGOT-SGPT), 42 per cent have biochemical evidence of chronic active liver disease and two per cent have subacute and active cirrhosis. There is an annual attack rate of Hepatitis B disease of 3.5 per cent and Hepatitis B antibody titres are present in 84 per cent. This asymptomatic liver disease requires close monitoring for clinical significance.


Treatment of the neurogenic bladder with direct current on the spinal cord (Myelotron). We carried out urodynamic examinations before and after galvanotherapy (Myelotron) of the spinal cord in 25 patients with upper and lower motor neuron lesions, mixed lesions and sensory lesions of the bladder. With the upper motor neuron lesions (neurogenic unhibited bladder, dyssynergia) there was a deterioration of the condition and therefore electrotherapy is contraindicated in this group of patients. With the lower motor neuron lesions and also the sensory lesions definite success was achieved with electrotherapy. Where there is a deficiency of impulses, it would appear to be compensated.


Intermittent biphasic surge stimulation of the pelvic floor: a preliminary report. A modification of the anal plug pelvic floor stimulator has been designed for the treatment of incontinence particularly due to bladder dysfunction. Using a surging intermittent train of impulses, the frequency and pulse width of which are 'tuned' to the individual patient, improved patient comfort and acceptance has been achieved. This has been partly due to the reduction or elimination of local electrolysis or electrophoresis.


Urinary incontinence: two cases of electronic stimulation after failing the Leadbetter technique. Two cases of urinary incontinence treated by electrical stimulation after failing the Leadbetter technique are presented. Both were first seen bearing imperforated anus. They suffered several operations for correcting this pathology and further attempting to relieve complete urinary incontinence. After a trial with intrarectal stimulation one of them received an implant. The other continued to use the anal plug. In both cases the result has been satisfactory. Cine radiological documentation of the sphincteric action of the stimulated muscles was performed.


[Effect of antilymphocyte serum on the course of influenzal infection in mice]. The effect of antilymphocyte serum (ALS) on the course of infection produced by influenza A/PR8/34 virus in mice weighing 10-12 g was studied. Inoculation of mice with ALS produced a longer persistence of influenza virus in the lung tissue and in the blood (up to 15 days of the observation period), whereas in the controls no influenza virus could be isolated after 9 days. No antibody production in ALS-treated mice was observed. The immunosuppression in mice reduced the extent of involvement of the lungs and lethality as compared with the control animals, being conducive to the change of the acute influenza infection into chronic one.


[Clinical value of rectal digital examination in early diagnosis of colorectal cancer (author's transl)]. A prospective study was carried out on a series of 1500 patients of a gastro-enterological and surgical unit in order to evaluate critically the accuracy of rectal digital examination as a single tool in the early diagnosis of colorectal tumours. The patients in this study were explored independently by two investigators, first by rectal digital palpation and afterwards by means of the proctosigmoidoscope. Endoscopy confirmed the presence of 239 tumours, 96 of these being diagnosed histologically as carcinoma. Comparative analysis of the results of physical and endoscopic examination demonstrated that digital palpation provided a correct diagnosis in 58 out of 239 tumours, equivalent to an accuracy of 24.3% for tumours within the reach of the rectoscope, and 10% for all colorectal tumours. Hence, rectal examination should not be used as single diagnostic tool in screening for large bowel cancer. A multiphasic screening system, including investigations for occult blood, proctosigmoidoscopy, endoscopic polypectomy and determination of colon-embryonic-antigen levels is discussed to obtain better results in general health screening, early diagnosis and avoidance of incurable colorectal carcinomas and the early detection of recurrence.


[Lupus erythematodes visceralis and age. Part 1: Lupus erythematodes visceralis as model of an autoimmune process and its relationship to age with special reference to antinuclear factors in different age groups]. This investigations show the lupus erythematodes visceralis as a modell of autoimmune processes. There are discussed the relations to age under special aspects of antinuclear factors in several groups of age.


[Lupus-erythematosus-like syndromes].

[Lupus-erythematosus-like syndromes]. Report on 3 patients with lupus-erythematosus-like syndromes, in which antinuclear antibodies in high titres and peripheral (or homogeneous) pattern--the characteristic leading immunologic phenomenon of SLE--could not be observed. The second patient suffered from the so-called pseudo-LE-syndrome described by Maas and Schubothe and characterized by antimitochondrial antibodies in high titres. The disease of the 3rd patient was explained as drug-induced LE-syndrome by Ovosiston. The variety of the antigens and antibodies directed against them, the improved diagnostics as well as the increased consumption of drugs were taken as reasons for the growing frequency of such LE-like syndromes. The coexistences, overlappings and transitional forms among the special autoimmune diseases render the diagnostics more difficult and explain the great variety of pictures of the SLE.


[Determination of isoenzymes of alkaline phosphatase and alpha-amylase in feces]. Investigations for the proof of isoenzymes of the alkaline phosphatase and the alpha-amylase in stool were carried out. The measurements of the faecal enzyme activities were performed in 96 patients with intestinal diseases. The disc electrophoresis in the polyacrylamide gel served for the separation of isoenzymes. The separated enzyme bands of the extracts of stool were compared with those ones of serum duodenal juice and extracts of the mucous membrane of the duodenum, the jujunum, the ileum as well as of the colon. Hereby up to 4 very much anodically wandering bands were present, which might be subunits or fission products of the alkaline phosphatase. In the alpha-amylase up to 5 bands could be proved, which were compared with those ones of the serum, the duodenal juice and the urine. A coordination of these isoenzymes concerning their origin is not possible. The faecal activities of enzymes correlate with the weights of stool. In exocrine pancreatic insufficiency and ulcerous colitis increased faecal activities of enzymes are found, the genesis of which is discussed.


Variation of lymphocyte classes and their PHA-P reactivity with age. Absolute and relative values of lymphocyte classes in peripheral blood of 19 to 80 year-old, apparently healthy donors were determined simultaneously by means of the cytocentrifuge method. Lymphocytes were classed as cells which formed rosettes with neuraminidase-treated sheep erythrocytes (T cells), as cells which bound C3b-loaded zymosan particles (B cells), or those which showed both characteristics (doubly marked cells = D cells). Cells which exhibited none of the above characteristics were classed as O cells. The reproducible absolute valued of T, B, D, and O cells showed a statistically significant decline with age, similarly to a decline in the total lymphocyte counts. The relative values in per cent, however, remained constant over the whole age spectrum. In 1 hour experiments, the acid phosphatase activity of non-stimulated and of PHA-P-stimulated cells decreased with age, the latter, however, less than did the controls. Therefore, the stimulating effect increased significantly. When cells were stimulated for a period of 4 hours, the stimulating effect decreased with age, indicating an age-dependent loss of longer lasting reactivity to PHA-P controlled by acid phosphatase activity.


Von Willebrand's disease in a Papua New Guinean. An example of von Willebrand's disease in a Papua New Guinean female is described; this is believed to be the first time that this disorder has been documented in a Melanesian. Some salient features of the diagnosis and management of the disease are discussed. Bleeding disorders in Papua New Guinea have been found with increasing frequency in recent years, and it is not unreasonable to expect that their true incidence will be similar to those seen elsewhere.


Hemorrhage in pancreatic pseudocyst presenting as massive gastrointestinal bleeding. Report of a case. A case of hemorrhage in a pancreatic pseudocyst presenting as massive gastrointestinal bleeding is reported. In the event of an unexplained GI-bleeding in an alcoholic this diagnosis should be considered. Selective angiography during bleeding may lead to correct diagnosis.


Pubertal manifestation of sex difference in circadian rhythm of corticotrophin-releasing activity in the rat hypothalamus. Post-natal development of the circadian rhythm of hypothalamic content of corticotrophin-releasing factor (CRF) was examined in male and female rats, separately. CRF activity was estimated by the intrapituitary injection technique. The circadian rhythm of the CRF content observed at the third week was without any noticeable sex difference: both male and female rats began their circadian rhythm with higher values in the afternoon than in the morning. Male rats maintained this pattern up to maturity. In contrast, female rats showed a marked change at ages of fifth to sixth week: the CRF rhythm in female rats changed to a female pattern, with higher values in the morning than in the afternoon. During this period, the vaginal opening occurred concurrently with a marked afternoon rise in the plasma corticosterone, characteristic of mature female rats. On the other hand, no essential difference could be observed between male and female rats in the developmental change in the circadian rhythm of locomotor activity. These results indicate that a sex difference in the CRF rhythm is not essentially related to the process of sex differentiation in the central nervous system, but is rather related to changes in ovarian activity following the onset of puberty.


Serum levels and alpha1-antitrypsin phenotypes in active pulmonary tuberculosis. alpha1-at phenotypes and serum levels were studied in 100 Greek patients of pulmonary TBC by starch-gel electrophoresis and radial immunodiffusion. The mean value of alpha1-at (315 +/- 77) was significantly lower (p less than 0.005) than in the control group. An attempt is made to explain this finding based on the alpha1-at phenotypes distribution in the TBC patients.


Intraamniotic and intramuscular administration of 15-methyl prostaglandin F 2alpha for midtrimester abortion. Two series of midtrimester abortion inductions are compared. In one series of 68 cases of midtrimester pregnancies (12-24 weeks), legal abortion was induced by one intraamniotic injection of 2.5 mg 15-methyl prostaglandin F 2alpha. Fetus was expelled in 67 cases (98.5%) after a mean time of 18.4 hours. One case with duplex failed to abort (1.5%). Abortion was complete in 54% of the aborted cases. In the second series of 93 cases abortion was induced by intramuscular injection of 300 microgram 15-methyl PGF 2alpha every third hour (the first dose was 200 microgram) during 30 hours. Fetus was expelled in 79 cases (85%) after a mean time of 16.7 hours. Failure occurred in 14 cases (15%). Abortion was complete in 57% of the aborted cases. Side effects (vomiting and diarrhea) were more frequent in the intramuscular series and very inconvenient to many of the patients. Excessive bleeding occurred more often in the intraamniotic series. A small rupture of the cervix was noted once (primigravida) in the intramuscular group. It is concluded that the intramuscular way of administration is a simple method of second trimester pregnancy termination with small bleedings but that otherwise it is inferior to the intraamniotic route.


The importance of rotatory proofs in the evaluation of a dizzy patient. In order to obtain an adequate functional evaluation of the vestibular system, we have to take into account the results of as well the caloric as the rotary tests. The discordance obtained in some cases, where a complete bilateral caloric areflexia is present whereas a conserved reactivity is confirmed by the rotationstimulus, argues against the merely application of the caloric stimulus. The opposite data obtained by both tests provide us information necessary to a good understanding of the functional state of our dizzy patient. Those cases where an unilateral hypo- or areflexia is detected by the calorics, may prove to be either "compensated" or not at the rotary stimulus. This functional datum is very important, as it informs us about the "Regulations-funktion", the central vestibular processing. Even in some cases only the rotary proof may indicate a dysequillibrium, which constitutes an objectivation of the dizzy state of our patient. The caloric DP, though it is a similar dysequilibrium, cannot substitute the rotary DP, this imbalance being of the same nature but not identical. We confirm and illustrate these argumentations by the statements in a series of 513 patients examined by a complex rotatory stimulationscheme.


Monoaminergic fluorescence in frog skin. The Falck-Hillarp fluorescence technique was employed in an attempt to determine the distribution of sympathetic innervation in frog skin. No evidence was found of a direct monoaminergic nerve supply to the cells of the non-glandular epithelium in the epidermis. Instead, specific fluorescence was mainly confined to the vicinity of the skin glands. Fluorescent fibers were observed surrounding the mucous type of gland. The secretory content of this gland was not fluorescent. In the granular type of gland the main source of fluorescence was the secretory granules filling the lumen. These developed a fluorescence in the spectral range of 5-hydroxytryptamine. The brightness of the fluorescence indicated a very high content of this amine. Fluorimetric analysis showed that no catecholamines were present in the secretion. In glands devoid of secretory granules there were some indications of a monoaminergic innervation of the secretory epithelium, but this was hard to determine because of the abundant nonspecific fluorescence. Sparse dots of specific fluorescence were found close to the surrounding smooth muscle cells. -- These findings rule out the possibility of a direct sympathetic nervous control of the non-glandular epithelium in frog skin but indicate that this is instead confined to the skin glands.


In vitro studies of frog mucous glands.

In vitro studies of frog mucous glands. The ionic outflow, mainly consisting of Na+ and Cl-, from the mucous glands in an excised nerve-skin preparation of frog has been determined by recording the conductance changes occurring in a fluid layer covering a small area of the skin surface. In the main series of experiments the glands were activated by stimulation of sympathetic nerve fibers in the skin nerve. The relationship between the ionic outflow and the number of nerve volleys was studied over a wide range. The outflow per impulse was found to be fairly constant during the first tens of impulses but diminished gradually with increasing number of stimuli up to a certain maximum value--varying in different preparations--after which the outflow ceased completely. During the initial phase of stimulation the outflow is most likely caused by an ejection of performed secretion due to the contractions of the glandular myoepithelium. The continued outflow in the later stages of the stimulation periods must be due to production of new secretion. Since the glandular epithelium is devoid of nerve terminals a nervous control of the ionic secretion can only be explained by an indirect influence mediated either by transmitter diffusion from the myoepithelial nerve endings or by a close electric coupling between the contractile and the secretory gland cells. Adrenaline and noradrenaline induce ionic outflows which like those evoked by nerve stimulation are inhibited by the beta-adrenoreceptor blocker propranolol, alpha-adrenoreceptor blockers being without effect. A serendipitous finding of tonus changes in the frog skin during nerve stimulation is also described.


In vivo studies of individual mucous glands in the frog. Individual mucous glands in the toe web were studied in curarized decerebrate frogs using vital microscopy in combination with still or motion photomicrography. By changing the focus position to different levels various structures in the gland could be identified and their changes during glandular activation studied. The first visible effect of nerve stimulation was a contraction of the myoepithelium and probably also structural changes of the secretory epithelium resulting in a narrowing of the glandular lumen. Following this, tricuspid valve opened and secretion was ejected. The latency and time course of the contractile response to nerve stimulation were determined and the influence of the number of stimuli on the duration of the contraction and relaxation phases was analyzed. Comparisons were made with reflex activation of the gland as well as with neurohormonal stimulation. The myoepithelial contraction was found to be under adrenergic control. Of the smooth-muscle stimulants tested only Substance P induced contractions. The time course of the ionic outflow from the toe web was determined by conductance measurements in the fluid surrounding the web and compared with the visually observed phenomena. The initial outflow was concomitant with the phasic myoepithelial contraction but a continued secretion could also be observed and recorded from glands kept in a steady state of contraction by iterative nerve stimulation. The functions of the toe web glands were found to be critically dependent on a maintained circulation in the surrounding capillary network.


Quantitative analysis of kanamycin ototoxicosis. The morphological changes after kanamycin intoxication of the inner ear, including both the cochlea and the vestibule, were quantitatively analysed by the surface preparation technique after succinic dehydrogenase staining. 75 guinea pigs were used. The outer hair cells in the basal coil and the inner hair cells in the upper coils of the cochlea were the most severely damaged, but many unusual modes of damage were also revealed. For example, the initial hair cell damage in the cochlea appeared in the upper hair cells. The clearly observed vestibular damage contradicts the general belief that kanamycin is not so toxic to the vestibular hair cells. The utricular macula and the lateral crista were most severely damaged. The delayed ototoxicity of kanamycin was observed for the first time in the vestibular hair cells.


Temporal lobe epilepsy. Follow-up investigation of 74 temporal lobe resected patients. This survey covers 74 patients with temporal lobe epilepsy, resistant to medication, who underwent unilateral temporal lobectomy during the years 1960-1969 at Rigshospitalet, Copenhagen. Preoperatively all patients were socially incapacitated. In all patients a unilateral or predominantly unilateral temporal EEG focus was found. No tumour or gross vascular malformation had been recognized before or during operation. At follow-up 45 patients were free from seizures. A further 15 had obtained a reduction in their seizure frequencies by at least 75%, while the remaining 10 survivors, only obtained a slight improvement or remained unchanged. There were four deaths. The operation also favourably influenced the psychiatric status, which was found closely related to relief from seizures. Prognostically favourable factors were: i) preoperative presence of a single type of seizure, ii) duration of epilepsy of less than four years, iii) operation in or before early adulthood, iv) an anterior temporal or sphenoidal electrode focus, or both, on the EEG. The prognostically unfavourable factors regarding complete relief from seizures were: i) preoperative presence of grand mal, ii) age at onset of epilepsy or of the first grand mal seizure between 5 and 19 years of age, iii) preoperative duration of epilepsy of over ten years and of grand mal of over one year. Prognostically unfavourable factors regarding psychiatric normalization were: i) preoperative presence of psychosis, ii) ictal-affective attacks or automatisms of a complex nature, iii) impairment of intellectual functions. The eventual neuropathological conclusion was that the more specific and circumscribed the histological abnormality the better the final outcome. The social rehabilitation was found to be significantly improved by operation at an early age.


Vertigo.

Vertigo. Vertigo reflects dysfunction in the vestibular system. Any disease state which changes the firing frequency of a vestibular end-organ and which produces unequal neural input to the brainstem causes vertigo. Caloric stimulation mimics acute end-organ dysfunction and helps establish the diagnosis.


Changes in saphenous veins used as aortocoronary bypass grafts. This report describes morphologic changes in saphenous veins used as aortocoronary bypass conduits, and discusses the relative contribution of various factors to these changes. The three primary changes are: (1) medial fibrous replacement, (2) adventitial fibrous proliferation, and (3) intimal fibrous proliferation. Medial fibrous replacement is caused by vein wall ischemia with loss of smooth muscle cells; adventitial fibrous proliferation is the result of organization of fibrin deposits and repair of ischemic injury; and intimal fibrous proliferation results from some stimulus, probably fibrin deposition on injured intima, which causes stimulation of smooth muscle cells to become fibroblasts or "myointimal cells". Although all grafts show some changes, the degree and severity of these three changes is variable along the length of the grafts and among separate grafts in the same patient.