Cytokine responsiveness in germfree and conventional NMRI mice. We have investigated the proliferative response of thymocytes from different mouse strains to cytokines in vitro. Interleukin 2 (IL-2), IL-4 and IL-7 induced proliferation of thymocytes from NMRI/KI (a locally bred NMRI mouse strain), NMRI/H ('traditional' NMRI mice), C3H/HeJ and C3H/HeN mice. NMRI/KI thymocytes showed the most prominent proliferation in response to IL-1 alpha and IL-1 beta. IL-3, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), inhibin and lipopolysaccharide (LPS) induced no thymocyte proliferation. Germfree NMRI/KI mouse thymocytes showed a significantly lower proliferation in response to IL-1 alpha and IL-1 beta than conventional mice. Rat tissues, previously shown to contain lymphocyte activating factors (LAFs), were also tested. Skin, tongue, esophagus, proventricular stomach, testis and placenta were all positive in the LAF assay utilizing NMRI/KI thymocytes, whereas none of the tissue extracts could induce proliferation in NMRI/H thymocytes. The higher cytokine responsiveness in conventional mice compared with germfree might suggest that exposure to microflora induces a higher state of activation of the immune system. The LAF assay, utilizing NMRI/KI thymocytes, is a highly sensitive IL-1 bioassay with a detection level of 1 pg/ml for IL-1 beta and 2 pg/ml for IL-1 alpha. The specificity of the assay is increased by utilizing NMRI/H mice to exclude the presence of IL-2, IL-4 and IL-7.


IL-1 synergizes with ARA-C in aborting the development of chloroleukemia while protecting from ARA-C-induced alopecia in the rat model. Recently, interleukin 1 (IL-1) was shown to protect rats from ARA-C-induced alopecia. The present study was designed to investigate the effect of combination rHu-IL-1 and ARA-C on transplantable chloroleukemia (C51) and at the same time evaluate the protective effect of IL-1 on the ARA-C-induced alopecia in the rat model. In vitro, IL-1 had no direct effect on growth, viability or differentiation of C51 cells, neither did IL-1 protect the C51 cells from ARA-C cytotoxicity. In vivo, the combination treatment of ARA-C + IL-1 aborted the development of transplanted chloroleukemia in 100% of rats, vs 60%, 10% and 0% survival for rats treated with IL-1, ARA-C and buffer respectively. All rates treated with ARA-C alone developed complete body alopecia. In contrast, none of the rats treated with combination IL-1 and ARA-C combination developed alopecia. Thus, IL-1 demonstrated a double beneficial effect, synergism with ARA-C against the leukemic cells on the one hand, and protection from ARA-C-induced alopecia, on the other.


Suppression of IL-2-induced SAA gene expression in mice by the administration of an IL-1 receptor antagonist. The hepatic acute phase response induced by the administration of interleukin (IL)-2 is most likely mediated by secondary cytokines. In this investigation, we examined the role of endogenous IL-1 in the synthesis of the hepatic acute phase protein serum amyloid A (SAA) during IL-2 treatment. The injection of IL-2 induced SAA gene expression in the liver. The concurrent administration of an IL-1 receptor antagonist (IL-1RA) markedly reduced hepatic SAA mRNA levels and, to a lesser extent, SAA protein levels in the serum. Although IL-1 is an inducer of IL-6 production, the administration of the IL-1RA had no effect on circulating IL-6 levels in IL-2-treated mice. These findings suggest that the production of IL-1 is an important factor in the induction of SAA mRNA in mice undergoing immunotherapy with IL-2.


Chronic intraperitoneal infusion of low doses of tumor necrosis factor alpha in rats induces a reduction in plasma triglyceride levels. Single and repeated bolus injections of tumor necrosis factor alpha (TNF) in laboratory animals have been reported to result in hypertriglyceridaemia, suggesting that TNF is a mediator of hypertriglyceridaemia occurring during infection. However, as during infection production of TNF is probably chronically elevated, we determined the effects of continuous infusion of low doses of TNF on plasma levels of triglycerides and cholesterol. Male rats, bearing a venous catheter to allow repeated blood sampling, were intraperitoneally equipped with osmotic minipumps which continuously delivered TNF or saline for 7 days. Infusion of rats with doses of TNF as low as 4.0 and 8.0 micrograms/24 h resulted in significant decreases in plasma levels of triglycerides as compared with those after saline infusion. Although plasma triglyceride concentrations were persistently lower in TNF than in saline animals throughout the study period, the differences were most prominent during the first days and reached statistical significance at day 1, 3, 4 and 5 and of the 4.0 micrograms experiment and on day 1, 2 and 3 of the 8.0 micrograms experiment. This suppression of plasma triglyceride concentrations was not accompanied by changes in plasma cholesterol levels. No effects of chronic TNF treatment on food intake, body weight change and rectal temperature of the animals were observed. These findings indicate that chronic infusion of low doses of TNF induces hypotriglyceridaemia in rats. The role of TNF as a factor in mediating hypertriglyceridaemia during infectious diseases needs to be reconsidered.


Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood: II. Application to rheumatoid arthritis and osteoarthritis. Rheumatoid arthritis (RA) is an immune disease in which the pathological immune reaction is thought to be initiated by the presentation of an (auto) antigen or superantigen by MHC class II positive cells to CD4 T cells. These successive immunological events can be studied by the cytokines produced at the different stages. Cytokine secretion by stimulated cells in autologous diluted whole blood has allowed the study of the immune profile characteristic of rheumatoid arthritis. The pattern of RA patient whole blood cells cultured in autologous blood is characterized by hyperactivity of the mononuclear cells with high secretion of IL-1 beta, TNF-alpha and IL-6 and low production of IFN-gamma, in comparison with the normal (N) and osteoarthrosis (OA) populations. The IL-2 secretion pattern is unique, arising from production followed by consumption. This production-consumption turnover is the most elevated in the RA group. The T cells are indeed activated in rheumatoid arthritis but regulatory events suppress some of their functions. A correlation was found between the inflammatory proteins and mediators of cellular immunity and macrophagic function: IL-1 beta and the sedimentation rate; IL-6 and fibrinogen; TNF-alpha and the number of blood monocytes. The secretion of OA-stimulated whole blood cells was similar to RA for two monokines (overproduction of TNF-alpha and IL-6) and different for IL-1 beta, not different from normal in OA. Stimulated whole blood cell cytokine secretion profile from RA and OA groups, was the same as previously observed in synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of surgery on in-vitro cytokine production by human monocytes. Surgery leads to significant modulation of the immune system, in which cytokines play a major role. Circulating interleukin 6 (IL-6) and IL-1 have been reported following surgery whereas tumor necrosis factor alpha (TNF-alpha) is only found in gut ischemia-associated surgery. We have investigated the consequences of surgery on in-vitro cytokine production by human monocytes stimulated by lipopolysaccharide (LPS) and staphylococcal toxic shock syndrome toxin-1 (TSST-1). Comparisons were made between the responsiveness of cells obtained the day before (D-1), during (D0) and after (D1, D2, D3) surgery. Patients undergoing abdominal aortic surgery (N = 9), carotid surgery (N = 4) and spinal surgery (N = 4) have been studied. A significant decrease of TNF-alpha, IL-1 beta and IL-1 alpha production by monocytes prepared from blood samples taken during the surgery was noticed, whereas IL-6 production was not significantly modified. On D2 a significant increase of monocyte responsiveness was observed and levels of cytokine productions rose back to initial values by the end of the follow up. The diminished in-vitro cytokine production observed during surgery might be the consequence of the effects of anaesthetic drugs, whereas the enhancement observed on D2 might reflect the surgical stress, leading to in-vivo priming of circulating monocytes.


High serum levels of TNF-alpha after its administration for isolation perfusion of the limb. In a phase II study, 18 patients with locally spreading melanoma or sarcoma of lower limb were treated by isolation perfusion (ILP) with hyperthermia and local infusion of high dose of recombinant human tumor necrosis factor alpha (rHuTNF-alpha) (4 mg). Bioactive TNF-alpha and interleukin 6 (IL-6) serum levels were measured serially. In the limb, TNF-alpha rapidly reached a plateau at 2 mu/ml, while IL-6 appeared later and progressively increased until the end of ILP. In the systemic circulation TNF-alpha rose up to a median concentration of 31 ng/ml after 1 hour, then decreased and became negligible after 6 hours. IL-6 peaked only after 5 hours after start of ILP (median: 36.7 ng/ml). In patients with substantial leakage towards systemic circulation, both cytokines peaked higher and earlier as compared with patients with minimal leakage. No correlation was found between cytokine levels and severity of side effects which in all cases were reversible. We conclude that high dose TNF-alpha infusion in ILP results in extremely high levels of bioactive TNF-alpha in the systemic circulation without irreversible side effect, and provokes a delayed blood release of large amounts of IL-6; there was a correlation between leakage from the limb during procedure and the magnitude of systemic cytokines levels.


Interleukin 8 (IL-8) in the bronchoalveolar lavage fluid from patients with the adult respiratory distress syndrome (ARDS) and patients at risk for ARDS. A sensitive and specific radioimmunoassay was used to measure interleukin 8 (IL-8) in bronchoalveolar lavage fluids from control subjects, patients with the adult respiratory distress syndrome (ARDS) and patients undergoing coronary bypass surgery, a risk factor for developing ARDS. Concentrations of IL-8, albumin, total protein and numbers of neutrophils were higher in both patient groups than in controls. Levels of IL-8 were significantly correlated with the influx of neutrophils, plasma protein extravasation and with the PaO2/FiO2 ratio. These data suggest that IL-8 may mediate the recruitment of neutrophils from the vascular compartment into the alveolar space and may therefore be an important determinant in neutrophil-mediated lung injury. Since increased levels of IL-8 were also found in BAL fluid from patients at risk in whom ARDS did not develop, other factors are likely to be involved and IL-8, as well as other markers of inflammation, are of little prognostic use.


Critical sites: a semantic approach to protein sequences. Application to the HIV-1 envelope molecule. We have designed two software systems allowing the study of proteins through a comparison to those stored in data banks. The first one, "Automat", locates in a systematic manner all identities shared by a given protein and the proteins in a data bank. The second, "Critic" enables the selection of specific segments in a given molecule by comparing them with those gathered in a data bank. These sites were termed "critical" since they mostly correspond to functional sites (active sites) of the well-known proteins which were studied with the aid of this program (somatostatin, insulin, IL2, etc). Automat allowed us to reveal homologies between HIV-1 and the CD4, which have remained unsolved until now. These similitudes proved to be critical sites (according to Critic). The putative involvement of these sites in the physiopathological processes as induced by HIV-1 are worth considering since the results of our experiments are consistent with this assumption.


Removal of gp160 induced bio-hazards for a safe AIDS vaccine candidate. In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system--anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1--particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp160 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs.


Cell-mediated immunity against HGP-30, a group-specific peptide of HIV p17 in individuals infected with the AIDS virus. HGP-30, the synthetic peptide analogue and active component in an HIV-1 (human immunodeficiency virus, type 1) p 17 core-based experimental vaccine, has previously been shown to induce cytotoxic and helper T-lymphocyte responses. In order to further define the T-helper cell responses which are known to play a role in enhancing the immunological response to foreign antigens, we studied the response of individuals infected with HIV to HGP-30 at various stages of disease progression. We have investigated the proliferative cellular response of peripheral blood mononuclear cells (PBMCs) derived from individuals infected with HIV-1 to HGP-30. We have found a PBMC proliferative response to HGP-30 in 40% of the healthy seroconverted patients, in 35% of the CDC stage III patients and in 18% of the CDC stage IV patients. There was no correlation between the proliferative response to HGP-30 and other antigens such as HIV-like proteins or tetanus toxoid not to CD4 cell count. HLA-DR typing revealed the possible presentation of HGP-30 by several different class II molecules. Since these class II molecules occur frequently in the general population, HGP-30 appears to contain broadly reactive epitopes and thus is not restricted as are many peptide vaccines. Due to its broad reactivity and extreme conservation in many HIV-1 strains. HGP-30 is one of the promising candidates for inclusion as a subunit vaccine against HIV-1.


Effect of enkephalins on bone marrow cells. Mouse bone marrow cells were incubated with methionine- or leucine-enkephalin (10(-15)-10(-6) M) before seeding into soft agar cultures. In marrow samples harvested at different times, enkephalins decreased GM colony count on average by 30-40%. In individual experiments, however, the same concentration of enkephalins caused even stimulation, or at other times had effect. In view of the circadian periodicity of neuroendocrine functions and hematopoietic activity, the enkephalin effect on bone marrow cells was tested on marrow samples harvested at fixed time points (6 am, 6 pm), using enkephalin concentrations in the physiological range (10(-12)-10(-9) M). The seeding efficiency of the 6-pm cell population was on average 50% above that of the 6-am population. The 6-pm cell population was also more susceptible to the inhibitory effect of the enkephalins (35% inhibition) than the 6-am population (15% inhibition), and the variability in response was considerably reduced. With progenitor cell-enriched population, obtained by fluorescence-activated cell sorting (FACS) of 6-am bone marrow samples, in 3 out of 6 experiments Met- and Leu-enkephalin showed 30-35% inhibition of GM colony formation over a wide range of concentrations (10(-15)-10(-6)). In the other 3 experiments, suppression as well as stimulation or no alteration in colony count were observed. This variability probably reflected quality (purity) of the progenitor cell population, and may indicate that the enkephalins affected hematopoietic cells via a population of accessory cells.


Bromazepam-induced dystonia.

Bromazepam-induced dystonia. Benzodiazepines are drugs with a good tolerance that are widely used for the treatment of anxiety. Extrapyramidal side-effects are unusual. Diazepam is effective for the treatment of drug-induced dystonias, nevertheless there are some reports of Diazepam-induced dystonia. We report a case history of a patient who developed oromandibular dystonia after taking Bromazepam. The possible mechanisms that cause drug-induced dystonia are described.


Allotransplantation of canine pancreatic islets. The complications of diabetes continue to present significant health risks despite improvements in conventional insulin therapy. Transplantation of pancreatic islet tissue has the potential to provide more precise glucose regulation and possibly minimize these implications. Recent advances in pancreatic islet isolation technology have facilitated investigation of islet allograft function in large animal models. These studies are fundamental to the development of methods for transplantation of allogeneic or xenogeneic islets in diabetic patients. This paper reviews the approaches which have been taken to prevent rejection and allow assessment of islet allograft function in the pancreatectomized dog model. These approaches include immunosuppression, immunomodulation of the donor tissue and isolation of allogeneic tissue within an immunoprotective membrane.


In vitro growth of erythroid progenitor cells (BFU-E) and production of burst-promoting activity (BPA) by T lymphocytes in patients with myelodysplastic syndromes. The in vitro growth of circulating erythroid progenitors (BFU-E) populations and the production of burst-promoting activity (BPA) by T lymphocytes have been studied in 17 patients with myelodysplastic syndromes. Based on the in vitro growth patterns of BFU-E, four groups of patients have been identified: i) normal BFU-E growth; ii) low spontaneous BFU-E growth, but normal response to LCM; iii) impaired BFU-E response to LCM; iv) no BFU-E growth. The pattern of BFU-E growth seems to be related to the clinical stage of the disease rather than to the FAB subgroup to which the patients belong. The ability of T lymphocytes to stimulate BFU-E growth was significantly reduced in all patients. The possible mechanisms inducing the impaired production of BPA by T lymphocytes are discussed. The in vitro evaluation of circulating erythroid precursors can supply useful prognostic information and possibly indications concerning the responsiveness of erythropoietic stem cells to recombinant human erythropoietin in vivo.


Radical tumor excision and cosmetic balance in the surgical treatment of breast carcinoma: biquadrantectomy. The present trend in favor of conservative surgery is in contrast with histopathological findings of multicentric breast carcinoma, which may be responsible for the occurrence of relapses in spite of the use of radiation therapy. As a consequence, conservative surgery appears to be inadequate, especially when tumor size exceeds 2 cm. Therefore for tumors up to 4 cm in size, which are not adherent to the pectoral fascia, we propose the excision of two quadrants with concomitant operation on the contralateral breast resulting in a more symmetrical and therefore cosmetic effect. This is a more radical procedure than the removal of the one quadrant.


Characterization of a murine monoclonal antibody, 5D-4, reacting with pancreatic cancers and islets of Langerhans. A murine monoclonal antibody (5D-4) was prepared by immunizing mice ip with human pancreatic cancer cell line (AsPC-1). The 5D-4 MAb reacted immunohistochemically with pancreatic and gastrointestinal tract tumors as well as pancreatic islets, and to a less extent with normal tissues. The 5D-4 MAb reacted not only with ca 50 KDa and 30 KDa solubilized protein from AsPC-1 cells by Western blot analysis but also with human insulin in a competition RIA. Double immunoperoxidase staining showed that the 5D-4 MAb cross-reacted with insulin but did not react with glucagon, somatostatin or pancreatic polypeptide. Immunoelectron micrograph of Langerhans island double-stained with the 5D-4 MAb and anti-insulin Ab revealed that the 5D-4 Mab recognized human insulin and ca 50 KDa and 30 KDa antigens in B-cells of islets of Langerhans. Thus, the 5D-4 Mab may be useful for the diagnosis of islet cell tumors as well as pancreatic cancers.


Thyroid hormone extraction by plasma exchange: a study of extraction rate. How to obtain an optimal efficiency of plasma exchanges in the treatment of severe hyperthyroidism has not been defined. In order to evaluate how long the exchanges must be continued to be fully effective in extracting thyroid hormones, we evaluated the extraction rate by repeated plasma sampling in two hyperthyroid patients and three euthyroid subjects who underwent a total of seven exchanges. Plasma concentrations of thyroid hormones were also determined just before, just after, and 24 hours following the exchange. The hormonal removal rate did not fall dramatically during the exchange, so that its efficiency--in terms of hormone extraction--depends closely on its duration. The determination of plasma thyroid hormone concentrations after the exchange does not appear to be useful in evaluating the thyroid hormone loss since these concentrations may not change in spite of the hormonal extraction.


Should there be a separate code of nomenclature for the protists? The present Botanical and Zoological Codes of Nomenclature are often inadequate for resolution of all the peculiar problems caused by the very nature of the numerous and diverse groups of the so-called 'lower' eukaryotic organisms known as protists. Whether or not a separate code should therefore be created for these species--many but not all of which are unicellular in structure and microscopic in size--is complicated by several factors. The principal one is related to the wide dispersal of protists throughout many taxonomic classes and phyla/divisions; sometimes even multiple kingdoms are involved. If recognition of a single kingdom Protista is no longer tenable, then even the concept of one code per kingdom is not applicable. Other difficulties arise primarily from long-standing differences in major provisions of present Botanical and Zoological Codes. Numerous 'ambiregnal' forms exist, species currently under dual code jurisdiction. The matter of names for suprafamilial taxa of protists, irrespective of their ultimate kingdom assignment, poses another set of concerns not yet resolved. A plea is made to recognize the legitimacy of having distinct high-level ranks for protist species that seem to be widely separated phylogenetically from fellow protists or from other eukaryotic assemblages.


When is a family not a family?

When is a family not a family? Recent molecular investigations of the small-subunit rRNA gene sequences have indicated that established taxonomic hierarchies can be clearly at odds with the degree of evolutionary divergence (as inferred from molecular divergence) between supposedly equivalent taxa at every rank (i.e., species through class), both within and across biological divisions. This is particularly true between the Rhodophyta and the Phaeophyta, whose higher-order taxa appear under- and overinflated, respectively. We present two plausible alternatives that algal taxonomists might adopt in order to invoke discussion on their relative merits.


Detecting morphological convergence in true fungi, using 18S rRNA gene sequence data. For the true fungi, phylogenetic relationships inferred from 18S ribosomal DNA sequence data agree with morphology when (1) the fungi exhibit diagnostic morphological characters, (2) the sequence-based phylogenetic groups are statistically supported, and (3) the ribosomal DNA evolves at roughly the same rate in the lineages being compared. 18S ribosomal RNA gene sequence data and biochemical data provide a congruent definition of true fungi. Sequence data support the traditional fungal subdivisions Ascomycotina and Basidiomycotina. In conflict with morphology, some zygomycetes group with chytrid water molds rather than with other terrestrial fungi, possibly owing to unequal rates of nucleotide substitutions among zygomycete lineages. Within the ascomycetes, the taxonomic consequence of simple or reduced morphology has been a proliferation of mutually incongruent classification systems. Sequence data provide plausible resolution of relationships for some cases where reduced morphology has created confusion. For example, phylogenetic trees from rDNA indicate that those morphologically simple ascomycetes classified as yeasts are polyphyletic and that forcible spore discharge was lost convergently from three lineages of ascomycetes producing flask-like fruiting bodies.


Green algae and the evolution of land plants: inferences from nuclear-encoded rRNA gene sequences. Phylogenetic analysis of 381 informative sites in partial sequences of nuclear-encoded large and small subunit ribosomal RNAs from 38 chlorophyll a- and b-containing plants (Chlorobionta sensu Bremer) including tracheophytes, bryophytes, charophytes and chlorophytes, supports the hypotheses of: (1) monophyly of the green plants (excluding Euglenophyta); (2) monophyly of the embryophytes; (3) non-monophyly of the bryophytes; (4) monophyly of the tracheophytes; and (5) a single origin of embryophytes from charophycean green algae. The Charales and Klebsormidium appear to be the green algae most closely related to the land plants. The unexpected basal divergence of Coleochaete and the apparent non-monophyly of the Zygnematales are not robustly supported and, thus, are interpreted to be sources of new questions, rather than new phylogenetic hypotheses.


An analysis of partial 28S ribosomal RNA sequences suggests early radiations of sponges. Sequences from the 5' end terminal part of 28S ribosomal RNA were obtained and compared for 22 animals belonging to all diploblastic phyla and for a large number of representatives of triploblastic Metazoa and protists. Phylogenetic analyses undertaken using different methods showed deep radiations of phyla such as Ctenophora, Cnidaria and Placozoa but also for groups of Porifera of low taxonomic rank. Short internodes between these radiations suggested an early rapid diversification of diploblasts. A long internal branch preceding the diversification of all triploblasts analyzed could be explained either by a long period with a single ancestor or by the extinction of the earliest triploblastic radiations. Finally some unexpected relationships were revealed among Porifera.


Quantization test of the evolution trend of Paleocosta pervinquieri (Ostracode) during a 10-million year period (Djebel-Dyr section, Paleogene, Algeria). Using a computerised technique that estimates differences or changes in the pattern defined by the distribution of 24 pore-canals of left valves of Paleocosta pervinquieri (Ostracode), we can speculate about the phylogenic evolution of the species ranging in age from Danian (66 My) to Ypresian (54 My) from the Djebel-Dyr section (North East of Algeria). This method is combined with traditional biometric and statistical studies and the analysis of architectural patterns of shells. Firstly, it reveals that Paleocosta pervinquieri is individualised in 6 morphs which evolve from the 'libyaenisis morph' to the 'mokkatamensis morph', between the P1 zone (66 My) to the P4 zone (56 My). During the P5 zone (55 My), we suggest that there has been a genation between the Paleocosta pervinquieri 'mokkatamensis morph' and the Reymensticosta sp. 'semi-reticulated morph'. Furthermore, the Theta-Rho method could be adapted and used for numerous paleontological and biological studies.


Miocene variability of Calcidiscus gr. leptoporus and possible evolutionary relationship with another Coccolithaceae: Umbilicosphaera gr. sibogae. Bibliographic data concerning the variability of coccosphere and coccoliths during the life-cycle of two extant Coccolithophorid species (Calcidiscus gr. leptoporus and Umbilicosphaera gr. sibogae) are summarized and completed by new observations on the structure of the proximal shield by fossil coccoliths. Thorough investigation of the proximal shield of C. gr. leptoporus in the latest Miocene (Messinian) assemblages from three oceanic localities (central Pacific, eastern equatorial Atlantic and southwestern Indian oceans) indicates the co-occurrence of two types of coccoliths: (1) typical C. gr. leptoporus and (2) specimens constituted by a distal shield similar to that of C. leptoporus, but with a proximal shield comparable to that of U. sibogae, although no typical U. sibogae occurs on the basis of the distal views. Such intermediate coccoliths have been previously described from the Badenian (middle Miocene) of central Europe. Whereas the authors considered them as a new species (Cycloperfolithus carlae), they are interpreted here as transitional morphotypes revealing an evolutionary link between C. gr. leptoporus and U. gr. sibogae, during the late Miocene. Consequently, the palaeontological 'species' carlae is hereby transferred to the genus Calcidiscus. These observations also point out the possibility of a diachronous evolution of the two shields of the same coccolith type, underlining the necessity for a better knowledge of the proximal shield structure, usually somewhat neglected.


The impact of environment on ontogenesis variations in Ruggieria and Chrysocythere (Ostracoda). The ontogenetic development of Ruggieria lekkii, Ruggieria triangulata, Ruggieria martinsoni and Chrysocythere ornata (Ostracoda) was investigated on two different continental shelves (Congo and Senegal). For one species, the ontogenetic trajectories obtained through length and height of valves differed considerably in distinct areas. In the first case, trajectories showing well-separated development stages and slight intraspecific variability in length and height were seen. In the second, trajectories showing valves which are difficult to relate to one stage or another and a high intraspecific variability were noted. In the latter, the uncertainties in the determination of the development stages were resolved by using a statistical method. Furthermore, this allowed for the comparison of the variations in ontogenesis (augmentation or reduction in the development), in relation to abiotic (detrital supply and upwelling processes) and biotic ecological factors (faunal density and interspecific competition). Comparisons were also made with ornamental variations observed on Chrysocythere ornata, which are directly linked with bioprecipitation (environmental) conditions. This comparison highlights the role played by abiotic and trophic factors on the developmental variations of ostracods in some continental shelves areas. This work shows that ontogenetic variations depend either on biotic or abiotic factors. They can act in different ways on distinct species and one can be predominant in a particular biota. Once the architectural characters have appeared, their variations no more depend on ontogenetic development. The study of ontogenesis reveals the adaptation capacities of one species in an environment with variable conditions.


Unusual extrusive organelles in karyorelictid ciliates: an argument for the ancient origin of this group. The karyorelictid ciliates never possess extrusomes that are typical of most other ciliates, i.e. trichocysts, mucocysts, and toxicysts, but instead present unusual types of extrusive organelles, most existing nowhere else. These organelles are: (1) Nematocysts with a filament making only 2-3 coils in the longitudinal plane, in Remanella multinucleata; (2) 'Orthonematocysts' with a short straight internal filament, in Remanella rugosa and R. brunnea; (3) Tiny bottle-shaped organelles somewhat resembling haptocysts, in Remanella granulosa; (4) Rhabdocysts, arrow-shaped extrusomes somewhat resembling certain trichocysts but undergoing no strong elongation during extrusion, in species of Tracheloraphis and in Kentrophoros latum; (5) Ampullocysts, complex vesicular organelles with hyaline secretion, occurring in Kentrophoros latum; (6) pigmentocysts or extrusible pigment granules, often with some internal structure, in almost all karyorelictids (Trachelocerca, Tracheloraphis, Trachelonema, Loxodes, Remanella, Geleia). This is the only type of cortical organelles the karyorelictids share with other ciliates, namely, the Heterotrichida (Stentor, Blepharisma). This highly aberrant set of extrusomes in karyorelictids argues that they are a very ancient branch of ciliates which separated from the main trunk early in evolution, conserving or developing an unusual set of extrusomes independently from the rest of ciliates. There is also some evidence for the relatedness of the Karyorelictida to Heterotrichida, already supposed from studies of the ciliary fibre systems and sequencing of ribosomal RNAs.


Flagellar apparatus duplication and partition, flagellar transformation during division in Entosiphon sulcatum. Electron microscopic examination of serial sections of developmental stages of the flagellar apparatus during the cell cycle indicates that the basal bodies replicate in a semi-conservative manner and that there is a flagellar transformation over two cell cycles in euglenoids as in other algal flagellate groups. Two new pairs of basal bodies are formed, each pair comprising one parental and one newly developed basal body. There is a transformation of the parental dorsal flagellum containing a thin paraxonemal rod into a ventral flagellum bearing a large paraxonemal rod. Observation of the roots associated with the basal bodies shows that the dorsal root transforms into an intermediate root over two cell cycles following the transformation of the dorsal basal body/flagellum to a ventral one. Also the two ventral roots are newly formed in relation to the formation of two new phagotrophic apparatuses during the division. After the breakage of the connection between the parental basal bodies the two new pairs move apart and are guided/drawn by transverse microfibrillar bundles which connect them to opposite sides of the pellicle. The axis of the separation/migration of the pairs of basal bodies is parallel to the axis of elongation of the dividing nucleus.


Energy metabolism of ancestral eukaryotes: a hypothesis based on the biochemistry of amitochondriate parasitic protists. Parasitic amitochondriate protists, representatives of early branches of eukaryote evolution, differ considerably in their central, energy metabolism from mitochondrion-bearing cells. These differences are: significant metabolic functions of inorganic pyrophosphate, major role of iron-sulfur proteins in key metabolic steps and in hydrogenosome-bearing organisms the disposal of electrons by H2 formation. Cytochrome-mediated electron transport and electron transport-linked phosphorylation are absent. All proteins which have been sequenced so far were found to be homologous to isofunctional proteins from other organisms. A few reactions, however, are catabolized by proteins which are not homologous to enzymes performing similar reactions in other eukaryotes. Two significantly different types of metabolism of amitochondriate protists can be distinguished: (a) without compartmentation and (b) with cytosol/hydrogenosome compartmentation. It is likely that these metabolic types have conserved certain traits present in ancestral eukaryotes before mitochondria became established.


Matrix representation in reconstructing phylogenetic relationships among the eukaryotes. The application of the method of matrix representation (MRP) addresses several problems associated with reconstructing phylogenetic relationships among composite organisms such as the eukaryotes. By allowing multiple molecular-sequence and non-molecular data sets to be combined into a single, relatively compact matrix for joint analysis, MRP addresses problems associated with the depth, diversification and specialization of eukaryotic lineages. Characters whose distributions may have been affected by endosymbiotic lateral transfer can be identified by compatibility analysis of MRP-generated hybrid matrices. In conjunction with variant-filtering techniques, MRP can be used to map patterns of lateral transfer in a given phylogenetic tree. These applications are illustrated with molecular-sequence and non-molecular data sets for eukaryotes.


Eukaryote-eukaryote endosymbioses: insights from studies of a cryptomonad alga. It has been proposed that those plants which contain photosynthetic plastids surrounded by more than two membranes have arisen through secondary endosymbiotic events. Molecular evidence confirms this proposal, but the nature of the endosymbiont(s) and the number of endosymbioses remain unresolved. Whether plastids arose from one type of prokaryotic ancestor or multiple types is the subject of some controversy. In order to try to resolve this question, the plastid gene content and arrangement has been studied from a cryptomonad alga. Most of the gene clusters common to photosynthetic prokaryotes and plastids are preserved and seventeen genes which are not found on the plastid genomes of land plants have been found. Together with previously published phylogenetic analyses of plastid genes, the present data support the notion that the type of prokaryote involved in the initial endosymbiosis was from within the cyanobacterial assemblage and that an early divergence giving rise to the green plant lineage and the rhodophyte lineage resulted in the differences in plastid gene content and sequence between these two groups. Multiple secondary endosymbiotic events involving a eukaryotic (probably rhodophytic alga) and different hosts are hypothesized to have occurred subsequently, giving rise to the chromophyte, cryptophyte and euglenophyte lineages.


The four genomes of the alga Pyrenomonas salina (Cryptophyta). Cryptomonads are a group of unicellular eukaryotic algae with unusual features. First, their plastids are surrounded by four membranes and second, between the two pairs of membranes there is a plasmatic compartment. This supernumerary eukaryotic compartment of the cryptomonad cell is devoid of mitochondria but contains starch grains, 80S ribosomes and a small vestigial eukaryotic nucleus called the nucleomorph. Isolation and characterization of the four genomes (from mitochondrion, plastid, nucleus and nucleomorph) of one cryptomonad, Pyrenomonas salina, demonstrates that the cryptomonads have originated from an unicellular organism related to green algae which endosymbiotically took up a eukaryotic protist related to the red algae.


Gene phylogenies and the endosymbiotic origin of plastids. The endosymbiotic origin of chloroplasts from cyanobacteria has long been suspected and has been confirmed in recent years by many lines of evidence. Debate now is centered on whether plastids are derived from a single endosymbiotic event or from multiple events involving several photosynthetic prokaryotes and/or eukaryotes. Phylogenetic analysis was undertaken using the inferred amino acid sequences from the genes psbA, rbcL, rbcS, tufA and atpB and a published analysis (Douglas and Turner, 1991) of nucleotide sequences of small subunit (SSU) rRNA to examine the relationships among purple bacteria, cyanobacteria and the plastids of non-green algae (including rhodophytes, chromophytes, a cryptophyte and a glaucophyte), green algae, euglenoids and land plants. Relationships within and among groups are generally consistent among all the trees; for example, prochlorophytes cluster with cyanobacteria (and not with green plastids) in each of the trees and rhodophytes are ancestral to or the sister group of the chromophyte algae. One notable exception is that Euglenophytes are associated with the green plastid lineage in psbA, rbcL, rbcS and tufA trees and with the non-green plastid lineage in SSU rRNA trees. Analysis of psbA, tufA, atpB and SSU rRNA sequences suggests that only a single bacterial endosympbiotic event occurred leading to plastids in the various algal and plant lineages. In contrast, analysis of rbcL and rbcS sequences strongly suggests that plastids are polyphyletic in origin, with plastids being derived independently from both purple bacteria and cyanobacteria. A hypothesis consistent with these discordant trees is that a single bacterial endosymbiotic event occurred leading to all plastids, followed by the lateral transfer of the rbcLS operon from a purple bacterium to a rhodophyte.


The number of symbiotic origins of organelles. Mitochondria and chloroplasts both originated from bacterial endosymbionts. The available evidence strongly supports a single origin for mitochondria and only somewhat less strongly a single, slightly later, origin for chloroplasts. The arguments and evidence that have sometimes been presented in favor of the alternative theories of the multiple or polyphyletic origins of these two organelles are evaluated and the kinds of data that are needed to test more rigorously the monophyletic theory are discussed. Although chloroplasts probably originated only once, eukaryotic algae are polyphyletic because chloroplasts have been secondarily transferred to new lineages by the permanent incorporation of a photosynthetic eukaryotic algal cell into a phagotrophic protozoan host. How often this has happened is much less clear. It is particularly unclear whether or not the chloroplasts of typical dinoflagellates and euglenoids originated in this way from a eukaryotic symbiont: their direct divergence from the ancestral chloroplast cannot be ruled out and indeed has several arguments in its favor. The evidence for and against the view that the chloroplast of the kingdom Chromista was acquired in a single endosymbiotic event is discussed. The possibility that even the chloroplast of Chlorarachnion might have been acquired during the same symbiosis that created the cryptomonad cell, if the symbiont was a primitive alga that had chlorophyll a, b and c as well as phycobilins, is also considered. An alga with such a combination of pigments might have been ancestral to all eukaryote algae.


[The chemosensory support of feeding behavior in precocial and altricial mammals during ontogeny]. The development of the structure and function of chemosensory apparatus of the tongue of mature and immature mammals was studied by scanning electron microscopy and in behavioral tests. Heterochronic development of receptors structures of dorsal surface of the tongue was established. At birth the chemoreceptors of body and root of the tongue were relatively mature in morphological aspects (the number of taste buds with pore). Taste pores in buds of anterior part of the tongue were found immediately at birth in mature and at the third week of postnatal period in immature animals. Behavioral tests found functional immaturity of chemosensory structures. Immature pups were able to recognize flavoured solutions only on the 7-10 day of age, and preference-aversion reactions of mature pups appeared to the third day of age. The data obtained are discussed in the respect of different ways of adaptation to food contacts with environment of the pups of mature and immature animals.


[Atypical endplate miniature potentials in the frog neuromuscular junction after modification of the intercellular matrix and osmotic exposures]. In frog cutaneous-pectoris muscles the frequency of slowly rising atypical miniature endplate potentials (MEPPs) was significantly enhanced after collagenase (0.1%) treatment. Treatment with trypsin, hyaluronidase, hyper- and hypoosmotic solutions caused no changes in slowly rising MEPP (frequency in muscle fibers with intact acetylcholinesterase (AChE). Inhibition of AChE caused appearance of giant MEPPs. Acceleration of acetylcholine diffusion from synaptic cleft after treatment with hyaluronidase decreased giant MEPP frequency demonstrating their dependence upon nonhydrolyzed acetylcholine in synaptic cleft. The relation between slowly rising MEPPs and activity of synaptic Schwann cells in discussed.


[The structural dynamics of vagus influence on the heart rhythm in exposures directed at altering the acting acetylcholine concentration]. In 29 experiments on anaesthetized cats burst stimulation of peripheral cut end of right vagus nerve leads to synchronization of heart and vagus rhythm. Influence of proserine, pilocarpine and prolonged vagus stimulation upon extent of vagus chronotropic effect and its components--tonic and synchronizing--was investigated. In all cases changes of vagus chronotropic effect during this actions were caused by unidirectional shifts of tonic component. Extent of synchronizing vagus chronotropic influences did not depend on the changes of acetylcholine concentration.


[The effect of stimulation and blockade of the dopaminergic system on the choice of behavioral strategy by rats in the shuttle box]. Upon stimulation and blockade of dopaminergic system of rats in the shuttle box the correlation between the strategy of escape behavior and functional state of dopaminergic system has been found. The modulatory effect of these systems on the mechanism of the adequate choice is suggested.


[Adaptation to periodic hypoxia decreases ethanol consumption and abstinence-related damages to the internal organs during withdrawal in chronically alcoholized animals]. Adaptation to intermittent hypoxia in a hypobaric altitude chamber reduced two-fold ethanol consumption in chronically alcoholized rats and limited or eliminated abstinence syndrome. The effect of the adaptation was evident from prevented development of abstinence analgesia, enhanced alcohol consumption following deprivation, abstinence activation of lipid peroxidation in the liver, and release of hepato-specific enzymes fructose monophosphate and gamma-glutamyl transpeptidase into blood. At the same time adaptation prevented the fall of cardiac fibrillation threshold and pronounced disturbance of ventricular contraction and relaxation. The problem is discussed of using adaptation to intermittent hypoxia in the treatment for those forms of alcoholism in which abstinence plays the key role.


[Diaphragmatic blood flow in hypoxia and hypercapnia]. By means of ultrasonic method, used in acute experiments on cats with closed abdominal cavity under nembutal narcosis, we studied the linear and volumetric blood flow velocity in the left phrenic artery, vascular resistance, systemic blood pressure, lung ventilation, arterial blood gases during different degrees of hypoxia and hypercapnia. It was shown that hypoxia and hypercapnia resulted in a decrease of the phrenic artery vascular resistance and an increase of the blood flow in the phrenic artery, not always proportional to hypoxia and hypercapnia degree. The correlation of an increase of the lung ventilation with an increase of the blood flow in the phrenic artery depends on the factor causing activation of the diaphragm performance. Some extreme conditions (prolonged asphyxia, blood loss, the exposure to 3% O2) lower phrenic vascular resistance, providing maximal blood supply of the diaphragm.


[The content of mitochondrial and microsomal cytochromes in liver tissue in experimental drug-induced fatty hepatosis]. Fatty tetracycline-induced steatosis is shown to reduce levels of mitochondrial and microsomal cytochromes. A decrease of microsomal cytochromes in the liver of hypoxia-resistant animals was similar to that of hypoxia-sensitive ones. This decrease was different for hypoxia-resistant and hypoxia-sensitive animals: for the former only cytochrome a declined, in the latter case cytochromes c+, c1 and a.


[The role of noradrenaline in regulating myocardial oxidative metabolism in rats with different resistances to hypoxia]. The effects of noradrenaline infusion on the regulation of oxidative metabolism in isolated rat heart were studied. It appeared that functional and metabolic parameters of heart of non-resistant and high-resistant to hypoxia rats were different. Noradrenaline changed the balance between aerobic and anaerobic processes in rat heart. It is evident that heart adrenoreceptors are involved in regulation of oxidative metabolism responsible for individual resistance of rat heart to hypoxia.


[The correlation of energy-consuming and energy-synthesizing reactions in rat hepatocytes in different O2-deficient states]. It is shown that rat liver cells have different sensitivity to oxygen deficiency. Hepatocytes of highly resistant animals have higher viability and maintain higher ATP levels during acute hypoxia. The data obtained enable us to suppose that liver cells of highly resistant rats are more resistant to oxygen deficiency than nonresistant ones.


[The conjugation of preliminarily immunosorbent-immobilized 5B4D6 monoclonal antibodies with a chelating polymer]. A study has been performed to investigate the change in antigen-binding capacity of antibodies as a result of their interaction with chelating agents, and polymers under various conditions. It has been demonstrated that antibody immobilization on the sorbent preceded by the antibody conjugation with chelating polymer allows better maintenance of specific activity of 5B4D6 monoclonal antibodies. Such modification yields a 10-fold increase in the antibody-antigen binding as compared with a standard conjugation technique in a mixture.


[Ganglioside participation in the regulation of free-radical reactions in brain membranes]. The effect of monosialoganglioside GM1 on induced free radical reactions in the synaptosomal and myelin membranes induced by Fe(2+)-H2O2 system was studied. The formation of free radicals was determined by measuring luminol-dependent chemoluminescence. It was found that preincubation of the membranes with GM1 (10(-11)-10(-6) M) and 12 or 12-palmitate, 13-acetate phorbol ester (10(-7)-10(-6) M) or alpha-tocopherol (10(-6) M) results in the decrease of chemiluminescent response. The inhibiting effect of alpha-tocopherol (but not of other compound tested) takes place without any preincubation as well. When the effect of GM1 was studied over a wide range of GM1 concentrations, a biphasic kinetics was observed, the highest per cent of inhibition of chemoluminescence being found at 10(-8) M. The data obtained provide evidence that the inhibition of free radical reactions in the brain membranes by nanomolar concentration of GM1 is not due to its interaction with lipid radicals. The results suggested that the inhibiting effect of GM1 is mediated through signal transduction system.


[The effect of endothelin-1 on Na+/H+ metabolism in vascular smooth muscle cells]. The effects of endothelin on intracellular pH (pHi) were examined in cultured rat vascular smooth muscle cells (VSMC) using the fluorescent probe BCECF. Endothelin induced biphasic changes in pHi: initial decrease followed by a subsequent increase above the basal level due to activation of the Na+/H+ exchange. The elevation of pHi was slow and sustained, but depended on the dose of endothelin: IC50 was about 3 x 10(-8) M. Na+/H+ exchange inhibition by EIPA (10(-7) M) or by equimolar replacement of external Na+ by choline abolished the pHi increase by enhancing the first phase of cytoplasm acidification. Effects of endothelin were compared with the action of protein kinase C (PK-C) activator phorbol 12-13 myristate ester (PMA). PMA induced a monophasic slow and sustained increase in pHi. The treatments of VSMC with H-7 and staurosporine (PK-C) inhibitors prevented the pHi response to endothelin and PMA. These results suggest that protein kinase C may play an important role in mediating the effects of endothelin on Na+/H+ exchange in VSMC.


[Calpains and cathepsin D from the damaged myocardium: the role of iodothyronines]. Experiments on albino male rats have demonstrated that a single subcutaneous isoprenaline injection produces cardiac calpaine activation and lysosomal labilization in euthyroidized animals. A 10 micrograms/kg triiodothyronine dose and a 50 micrograms/kg L-thyroxin inhibit calpaines and stabilize myocardial lysosomal membranes in intact rats. The effects following myocardial damage do not occur or become less pronounced in hyperthyroidism. Triiodothyronine proved to be more effective.


[The competition of serum amyloid protein and apoprotein E for binding with human serum albumin]. The relationship between the concentration of serum amyloid protein (SAP) isolated from human serum and the parameters of the protein elution during gel-filtration and alos with the efficiency of Ca(2+)-dependent SAP binding with sepharose 4B was studied. The dissociation of the SAP oligomeric form in solution and the interaction of the protein with human serum albumin with fully reduced S--S bridges due to the introduction of the additional hydrophobic surface was shown. Apoprotein E isolated from human plasma very-low-density lipoproteins replaced SAP in the complex with albumin.


[The effect of sodium cyanate-modified hemoglobin oxygen affinity on the heat resistance of rats]. Regression analysis of relationship between rat hemoglobin-oxygen affinity (HOA) and rectal temperature has shown a close positive correlation of these parameters. Heat resistance (HR) was examined in rats with HOA elevated by sodium cyanate in order to recognize the contribution of HOA to a process of body heat adaptation. Our data suggest that HR of treated rats was larger than in control animals. These results are discussed in relation with antioxidant type of the cyanate elevation in HOA.


[The mechanisms of the neutrophil suppression of creatine kinase and aspartate aminotransferase activities in rat skeletal muscles]. Abdominal neutrophils effect on rat skeletal muscle m. soleus was investigated in vitro. The incubation was carried out in Hanks balanced solution within 24 hrs. It was a release of proteins from m. soleus 1 hr later. Creatine kinase (CK) and aspartate aminotransferase (AAT) activities increase was detected in incubation medium. The neutrophils released their proteins quicker than muscles. A dramatic inhibition of CK and AAT activities took place during coincubation of m. soleus and neutrophils. Zymosan-activated cells had a higher inhibition potency in comparison to nonactivated neutrophils. Analysis of proteinase and myeloperoxidase activities in incubation medium has given evidence that CK and AAT inhibition by non-activated neutrophils mainly depends on cell-secreted proteinases. Zymosan-activated neutrophil inhibition of CK and AAT consists of proteinases and myeloperoxidase effects. AAT appeared to be more resistant than CK to the damage by neutrophils. The used approach failed to demonstrate the direct damage effect of neutrophils on m. soleus, but the described enzyme inhibition mechanism can take place in vivo during leukocyte infiltration of skeletal muscles after intensive muscular activity.


[The anticoagulant properties of the endothelium studied by the standard venous occlusion test]. Venous occlusion (VO) during which thrombin (Th) is postulated to be generated is routinely used for evaluation of fibrinolytic potential of endothelium (E). This study was performed to find out whether VO can also be used for assessment of anticoagulant function of E. VO was performed in 98 male patients (pts) with ischemic heart disease. Levels of protein C (PrC) which is related to Th binding by thrombomodulin and fibrinopeptide A (FpA)--a marker of presence of free Th--were determined together with some other factors of coagulation and fibrinolysis. Differences between pre- and postVO PrC levels fluctuated from -54.8% to +57.3%. According to reaction of PrC to VO pts were divided into 2 groups: 13 pts with increase or no change and 17 pts with decrease (consumption) of PrC. In pts without PrC consumption there was a significant increase in FpA. In pts with PrC consumption FpA was unchanged. In pts with PrC consumption exceeding its median value for this group (14%) PAI-1 antigen level fell significantly (-8.4 + 4%) during VO. Thus PrC consumption after VO indicates that TH is effectively removed from blood stream by endothelial factors. Absence of consumption of PrC is a sign of ineffective anticoagulant function of E. Increase in PrC level during VO in some pts may be due to its escape from tissue depot.


[The action of dipyridamole on megakaryocytopoiesis in regenerating and stationary bone marrow cell populations]. The effect of dipyridamole on megakaryocytopoiesis in regenerating and stationary populations of mouse bone marrow cells has been studied by heterotopic transplantation of the bone marrow using histological, electron microscopic and biochemical techniques. It is shown that drug administration induced destruction of megakaryocytes. In megakaryocytic cytoplasm giant lipid granules were found whose growth and number increase resulted in megakaryocytes kill. Gas-liquid chromatography was used to evaluate the effect of dipyridamole on distribution of lipid fatty acids of the stationary and regenerating populations of the bone marrow cells. A marked increase of the percentage of docosahexaenoic acid was found in lipids of the stationary population. Chronic dipyridamole administration caused an increase of percentage of myristic, palmitic oleic acids, and decrease of percentage of arachidonic and eicosapentaenoic acids in lipids of regenerating bone marrow cells population.


[The action of korazol on the defensive behavior of rats]. The paper shows the dependence of behavioral changes provoked by corazol on individual characteristics of the animals. The rats with high activity in the ATS demonstrated the highest response to the drugs.


[The properties of the glucocorticoid-sensitive alkaline proteinases of target organs in rats]. The preliminary characterization of glucocorticoid-sensitive alkaline proteinases of rat thymus and liver was carried out. The role of active serine and cysteine residues in proteolysis was estimated. The influence of Ca++, Mg++, Fe++, Fe , Cu++, EDTA and EGTA on enzymes activity was studied. It is shown that alkaline proteinases of thymus and liver have similar properties, but are not completely identical.


[The normalizing effect of dalargin on the glucocorticoid and opioid levels of the blood in CBA and C57Bl/6 mice undergoing footshock stress]. Radioreceptor investigations showed that it is impossible to interpret changes in the activity of opioid receptor ligands of mu and delta types in plasma of mice under footshock stress (FSS) as activation or depletion of opioid system (OS). There occurred qualitative changes characterized by interstrain differences (ID). These are also typical for dynamics of development of FSS effects on blood corticosterone levels. Administration of dalargin diminishes qualitative and quantitative changes in OS function at different periods after FSS preventing early rise of corticosterone levels after the exposure. In spite of common features in dalargin action on opioid and steroid metabolism in mice of both strains, ID are also present.


[The hemodynamic and metabolic effects of 2-deoxy-D-glucose in waking Wistar rats]. The effect of 2-deoxy-D-glucose (2-DG) in a dose of 250 mg/kg as a stressogenic factor on changes in hemodynamic parameters and metabolism in awake rats was quantified during 6 hours. It was found that a single 2-DG injection causes lowering of blood pressure on min 40 and 120. Heart rate tended to slow down. Diminished glucose concentration in the brain observed on experiment minute 15 induced a number of adaptive reactions in the body. Epinephrine plasma levels increased sharply on min 15 and 40. Norepinephrine concentrations elevated slightly only at the beginning of the experiment. The maximal glucose level in blood plasma was observed on min 40 and 120 and that of lactate 40 min following 2-DG injection. The level of immunoreactive insulin rose. Glucose content in the heart came up sharply on min 15 and 40. Lactate concentration in the heart increased continuously.


[Antibody formation to morphine and neuromediators in morphinized rats]. The paper demonstrates induction of antibodies to morphine and neurotransmitters (dopamine, norepinephrine, serotonin) in rats treated with intraperitoneal injections of morphine hydrochloride during 2 and 4 weeks in increasing doses. A contribution of such antibodies to the mechanisms of morphine tolerance and formation of physical dependence is considered.


[The immunomodulating activity of new muramyl dipeptide derivatives in vitro]. The action of some new MDP derivatives on functional activity of murine T-lymphocytes and macrophages was studied. The following tests have been used: proliferation of spleen cells in one-way allo-MLC; IL-1 and TNF production by peritoneal macrophages treated with the preparations. The most expressed enhancement of lymphocyte proliferative response in MLC has been exerted by beta C7H15 MDP and beta C16H33 MDP (stimulation indexes 31-69%). beta C7H15 MDP, beta C16H33 MDP and polyacrylamide-MDP (P-MDP) alone or in combination with LPS caused elevated secretion of IL-1 by macrophages. While beta C7H15 MDP was as active as MDP, beta C16H33 MDP and P-MDP manifested increased ability to stimulate IL-1 production in comparison with MDP. beta C7H15 MDP, beta C16H33 MDP, P-MDP and MDP induced similar level of TNF production by murine macrophages. However, simultaneous treatment of macrophages with beta C16H33 MDP and LPS resulted in more significant enhancement of TNF production than combination LPS + MDP.


[A comparative study of met-enkephalin effects on the secretion by murine lymphocytes of antibodies to different antigens]. The influence of met-enkephalin on specific antibody production by lymphocytes from mouse lymph nodes was studied in vitro in productive phase of immune response. It was shown that the peptide did not influence secretion of IgM-antibody to T-independent antigen-trinitrobenzensulfoacidic group, but suppressed secretion of IgG-antibody to T-dependent antigens both during primary and secondary response. The efficiency of superlow concentrations of the peptide (10(-15)-10(-14) M) for the response to ovalbumin, but not for the response to bovine gamma-globulin was shown. All effects of met-enkephalin were naloxone-reversible. The existence of individual distribution in dose-dependences of peptide action on antibody secretion in response to ovalbumin was demonstrated.


[The immunostimulating properties of cholecystokinin octapeptide and its fragments]. Immunostimulating properties of cholecystokinin octapeptide (CCK-8) were evaluated in experiments on adult normal and thymectomized mice, in vitro. It was shown that CCK-8 stimulates IgM-PFC production to SRBC, but does not change the immune response to Vi-antigen. CCK-8 increases the number of Thy-I+ spleen T cells and restores thymus-dependent immune response in thymectomized mice. CCK-8 has no effect on neutrophil phagocytosis activity in vitro. The immunostimulating activity of CCK-8 is related mainly to C-terminal fragment (identical to pentagastrin tetrapeptide) since the N-terminal CCK-8 tetrapeptide displays negligible effect in all tests.


[Changes in the content of reduced glutathione in the liver of mice under the action of staphylococcal enterotoxin type A and lipopolysaccharide]. We investigated the level of reduced glutathione in mouse liver after injection of staphylococcal enterotoxin type A (SEA) and Serratia marcescens endotoxin (LPS). It was shown that SEA caused significant glutathione depletion. Glutathione level fell more under the combined treatment by both toxins. The data demonstrate a considerable role of antioxidant potential in the mechanism of enhanced sensitivity of animals to the lethal effect produced by LPS.


[The stimulation of the bactericidal activity of human neutrophils by lymphoid cells activated by interleukin-2; the effect of inflammatory cytokines]. Regulation of bactericidal activity of neutrophils (BAN) of healthy volunteer blood donors was studied. Interleukin-2 (IL-2)-activated lymphocytes potentiated BAN more effectively then resting lymphocytes. IL-2-activated mononuclear cells (containing lymphocytes and monocytes/macrophages) decreased neutrophil-potentiating activity when compared with nonactivated mononuclear cells. It was concluded that IL-2-activated monocytes exerted potent suppressive influence upon lymphocytes. Recombinant interleukin-1 beta, tumour necrosis factor-alpha, interferon-gamma acted synergistically with IL-2-activated lymphocytes on BAN when the level of neutrophil bactericidal activity was low.


[The effect of a mite allergen on Na/H metabolic activity in peritoneal mast cells]. Mite allergen interacting with mast cells treated with sera from bronchial patient sensitized to home dust Dermatophagoides farinae causes changes in intracellular pH. Regulation of pHi peritoneal mast cells is participated by Na/H metabolism probably activated by protein kinase C.


[A method for the primary biological assessment of the photodynamic activity of photosensitizers in a nontumor model in vivo]. In comparison with traditional laboratory methods of photosensitizers screening in vitro and in vivo on transplanted tumors, the proposed method of PDA evaluation has the advantages. Criterion of PDA is the quantitative characteristic--the area of photodynamic necrosis on the surface of laboratory mice liver 24 hours after combined action. According to the screening results, PDA of photosensitizers is distributed: AIPcS2-3 > AIPcS1 > Photofrin-2 > AIPcS3 > or = HpDChina > Fotosan-3 > Fotosan-2. Morphological research allows to characterize PDA of photosensitizers qualitatively. Thus, AIPcSx derivatives have more expressed cytolytic and nucleotropic effect on parenchyma cells (hepatocytes) in comparison with HpD derivatives.


[The oncogenic action of nonfibrous mineral dusts]. Nonfibrous mineral dusts antigorite, basalt, cement, zeolite-klinoptilolite and gamma-alumina were tested for carcinogenic activity in rat experiments. Intraperitoneal injections of zeolite-klinoptilolite and gamma-alumina led to development of peritoneal mesotheliomas, whereas antigorite and cement had no carcinogenic potential. There is no differences in physicochemical and chemical properties between carcinogenically active and inactive nonfibrous dusts. A new class of carcinogenic substances is defined including basalt, zeolite-klinoptilolite and quartz which belong to nonfibrous mineral dusts.


[Changes in the level of DNA synthesis in a culture of Ehrlich ascites tumor cells under the action of different concentrations of a chalone-containing preparation]. The study was made of the effect of various concentrations of chalone-containing preparation from ascitic Ehrlich tumor on DNA synthesis in the tumor. The preparation was shown to suppress DNA synthesis in dose-dependent manner. The dose dependence was characterized by the effect of saturation which is likely to reflect binding of chalone molecules with specific cell receptors.


[The characteristics of Ehrlich carcinoma recurrence and metastasis]. It was shown that surgical removal of Ehrlich carcinoma growing i. m. in male mice F1 (CBA C57Bl/6) does not entail longer survival in comparison with intact tumor-bearing mice (59.4 and 62.2 days, respectively). Postoperative relapses appear in 40-60% of the animals, metastases in 100% of animals. Metastases were not observed in intact tumor bearing mice. The second-challenge tumor was not observed in operated mice despite metastatic growth and recurrences of the same tumor. We suggest that metastatic growth depends on the tumor cell features and that this process is controlled by host organism.


[The chromosomal radiosensitivity of children whose parents were exposed to antitumor radiochemotherapy]. The effect of gamma radiation was studied on routine stained chromosomes from lymphocytes of children born to Hodgkin's disease patients after cancer therapy (CP) in comparison to children from healthy parents (HP). Irradiation (0, 0.25, 0.50, 1.00, 1.50 Gy) of the whole blood was performed in culture medium. Metaphases were obtained from 52-h cultures. Chromosomal aberrations were used as an endpoint. Aberrations of both chromosomal and chromatid types were scored in 150-200 metaphases for estimation of spontaneous level of cytogenetic injuries and in 100 metaphases of induced one. It is found that chromosomes of CP children are more radiosensitive than chromosomes of HP ones, the spontaneous frequency of chromosome aberrations being equal in both groups.


[A comparative analysis of the cerebral cortical proteins in rats with different sensitivities to hypoxia]. A comparative analysis of 339 protein fractions of cerebral cortex of rats both resistant and non-resistant to oxygen deficiency has been fulfilled by means of two-dimensional gel-electrophoresis. A specific group of 9 protein fractions with molecular weights in the range of 32-68 kD was found to be quantitatively changed under hypoxia influence. An activation of labile protein synthesis was a predominant response to acute hypoxia in the resistant rats, while the synthesizing processes in the non-resistant rats were rather weak. An adaptation to hypoxia mostly resulted in the decrease of quantitative representations of labile protein fractions and has been realizing in different ways in resistant and nonresistant rats. The data obtained seem to testify to the changes of protein synthesis under chronic hypoxia conditions in the cerebral cortex chiefly determined by fast adaptation mechanisms.


[A morphological evaluation of the action of collagenase from the king crab Paralithodes camtschatica on the experimental wound process]. The paper presents the results of experimental morphological evaluation of the effect of a new proteolytic enzyme collagenase of crab Paralithodes camtschatica on wound healing in infected and aseptic rabbit wounds. The enzyme was applied on wounds using gauze and gelevin. The findings show that this protease is highly effective for debridement of infected wounds, the effect increasing at gelevin addition. To reach maximal therapeutical effect and diminish the inhibition effect of collagenase on granulation tissue, it is recommended to reduce the dose of protease during debridement process. Clinical application of crab collagenase must be individual as well as duration of wound enzymotherapy.


[Structural changes in the central nervous system of dogs with a combined bilateral lesion of the carotid arteries]. In the experiment 20 dogs were subjected to bilateral kinking of the carotid artery and the effects were assessed angiographically and radiologically as well as changes in the cerebral cortex. It is shown that 30 degree kinking produced more significant ultrastructural changes which in most cases were reversible.


HIV-associated tuberculosis in developing countries: epidemiology and strategies for prevention. The association between tuberculosis and HIV presents an immediate and grave public health and socioeconomic threat, particularly in the developing world. In early 1992 WHO estimated that approximately 4 million people had been infected with both Mycobacterium tuberculosis and HIV since the beginning of the pandemic; 95% of them were in developing countries. The association between tuberculosis and HIV is evident from the high incidence of tuberculosis, estimated at 5-8% per year, among HIV-infected persons, the high HIV seroprevalence among patients with tuberculosis, the high occurrence of tuberculosis among AIDS patients, and the coincidence of increased tuberculosis notifications with the spreading of the HIV epidemic in several African countries. The impact of the two epidemics on resource-poor countries has ominous social and medical implications, and the already overstretched health services now have to face a tremendously increasing tuberculosis problem. HIV infection worsens the tuberculosis situation by increasing reactivation of latent tuberculosis infection in dually infected persons as well as by favouring rapid progression of new infections in the HIV-infected. This also results in an increase of the risk of infection and a subsequent increase of cases in the general population. In order to respond to this urgent problem, the highest priority must be given to strengthening tuberculosis control programmes in the countries where they are poorly developed and where the prevalence of HIV and tuberculosis infections is high. Besides improving the cure rate by early diagnosis and prompt treatment of patients with tuberculosis, two major strategies that need consideration include BCG vaccination and preventive chemotherapy among HIV-infected individuals. The latter strategy is considered as the most critical intervention that would help to limit the expected increase in clinical tuberculosis from the pool of HIV and tuberculosis coinfected individuals. However, a number of issues need to be addressed urgently and before such an intervention can be implemented in the developing countries.


Mass miniature X-ray screening for tuberculosis among immigrants entering Switzerland. Among 50,784 new immigrants entering Vaud Country, Switzerland, between 1988 and 1990, 674 abnormalities were discovered by mass miniature X-ray screening on arrival (424/43,803 foreign workers, 238/4512 refugees and 12/2469 foreign students). 2043 refugees had no radiological examination. After clinical examination, tuberculosis (TB) was considered the likely diagnosis in 256 cases, of which 132 were offered an antituberculous treatment according to the current recommendations of the Swiss Association against TB. 34 of the subjects were smear- or culture-positive (5% of all radiological abnormalities, 0.08% of all immigrants). Only 46 subjects had any clinical complaint. Among foreign workers, 0.18% were carriers of tuberculous lesions needing a treatment; the proportion was 1.22% among refugees. By ethnic origin, the proportion is highest among Africans (1.43%), followed by Turks (1.04%), subjects from the Middle East (0.62%), Yugoslavia (0.55%), Portugal and Spain (0.14%). Mass miniature X-ray screening for TB in immigrants from high prevalence countries entering Switzerland still detects a majority of asymptomatic cases and seems an easy means of preventing the transmission of TB to members of the same community.


Good concordance between two batches of new tuberculin in the Mantoux test. Two batches of new tuberculin prepared from different unheated cultures of M. tuberculosis, 8 years apart, were tested for concordant skin reactions in the WHO standard Mantoux test. Both batches T1327 and T1456 were simultaneously injected (0.1 ml) into the dorsal aspects of the forearms of 123 school children, aged 11-13 years, who had been BCG vaccinated at birth. The mean size of the induration to T1327 was 10.3 (SD 4.4) mm and to T1456 it was 11.3 (SD 4.2) mm. There was a significant linear correlation between the indurations caused by both batches (r = 0.91, P < 0.0001). The discrepancies between the readings were all within the limits of a 5 mm category. The mean size of the BCG scar was 8.1 (SD 4.8) mm, and there was a trend associating smaller BCG scars with smaller tuberculin responses which did not reach statistical significance. The two different batches of new tuberculin gave remarkably concordant results in WHO standard Mantoux testing illustrating the stability of the production process and suggesting that the results obtained in studies using different batches of new tuberculin are comparable.


Comparative study of skin testing with PPD and new tuberculins by the WHO Mantoux test. PPD RT 23 tuberculin and two batches of new tuberculin (NT) were tested for concordant skin indurations in the WHO standard Mantoux test in 11- to 13-year-old Finnish school children BCG vaccinated at birth. All were double tested with RT 23 and with either batch T1327 (614 children) or with batch T1456 (312 children) of NT. The results were compared with data available from an earlier study employing RT 23 and T1327 in Ethiopian children, 50/134 of whom had a BCG scar. The mean induration to RT 23 after 72 h was slightly smaller than to the NTs. The individual readings for RT 23 had significant linear correlations with T1327 in Finland (r = 0.77) and in Ethiopia (r = 0.89), and for T1456 (r = 0.83; P < 0.001 for all three). Zero reactions were much fewer to NTs (5.5% to T1327 and 0.3% to T1456) than to RT 23 in Finland (18.2% and 9.3% respectively for the two groups). The results were similar in Ethiopian children. Our results indicate that RT 23 and the two NTs give concordant results, but NTs seem to be more specific, perhaps because they retain more species-specific antigens. Analysis of our results suggests that different peaks in the distribution of reaction sizes were due to responses to different antigens or combinations of antigens, and in the case of the largest reactions, to a different type of immunological response.


Isoelectric focusing patterns of beta-lactamases in the rapidly growing mycobacteria. beta-lactamases from 259 strains of rapidly growing mycobacteria that included the third biovariant complex of Mycobacterium fortuitum, M. peregrinum, M. abscessus, M. chelonae, the M. chelonae-like organisms (MCLO), and M. smegmatis were analyzed by isoelectric focusing (IEF). All isolates produced acidic beta-lactamases with major band isoelectric points (pIs) between 4.4 and 6.0. Each of the 6 taxonomic groups exhibited 1 or 2 characteristic beta-lactamase IEF patterns. Heterogeneity among IEF patterns was evident in 5 of the 6 groups, however, and was greatest among the third biovariant complex of M. fortuitum. beta-lactamase patterns correlated with previously identified taxonomic subgroups of M. smegmatis and the third biovariant complex of M. fortuitum. beta-lactamase IEF analysis of MCLO strains isolated from two outbreaks demonstrated its possible usefulness for epidemiologic evaluation.


Tuberculosis surveillance and evaluation system in Portugal. Tuberculosis is an important public health problem in Portugal, so a new and improved computerized programme for the surveillance and evaluation of tuberculosis data was set up to obtain more precise information of relevant epidemiological indices, besides helping clinicians and regional coordinators to evaluate the local situation, such as clinical features, results of treatment and surveillance of failures and abscondings. Data stored on the computer is described in detail. The evolution of the incidence of tuberculosis is presented, together with more detailed figures for 1990. These figures were obtained with the former, cruder process. The present system is now being deployed and checked, after 1 year's trial and evaluation by some of its users. Its results will be presented in a future publication.


Childhood tuberculosis and tuberculous meningitis: high incidence rates in the Western Cape of South Africa. In recent years higher incidence rates of tuberculosis (TB) have been reported from the Western Cape than from other health regions of South Africa. In contrast to the various pulmonary forms of tuberculosis, tuberculous meningitis (TBM) always requires hospital admission, and can thus be used as an indicator of the extent of the infection in a community, as well as providing a measure of the effectiveness of primary and secondary preventive measures. In the present study an attempt was made to identify all cases of tuberculous meningitis aged 14 years and younger which occurred in the region, by checking notifications and the records of all hospitals, and verifying diagnosis against set criteria. Rates for the entire period were calculated according to updated census data. There was a total of 689 confirmed cases, of which only 55% had been notified. Of the 238 cases confirmed in the 3-years period, 1985-1987, 25.2% were under 1 year, 51.7% under 2 years, and 79.8% under 5 years of age. Age-specific incidence per 100,000 children were respectively 31.5 (0-1 years), 17.1 (1-4 years), 4.8 (5-9 years), and 0.7 (10-14 years). Rates in rural areas were far higher than in metropolitan regions. Utilizing tuberculin test data and total notifications, the following risks could be calculated for 'Coloured' children (of mixed race) aged 0-4 years: 2-3% annual risk of infection; 15.7% risk of TB in infected population; 0.5% risk of TBM in infected population; 0.9% risk of TB in children aged 5-14 years; 0.01% risk of TBM in children aged 5-14 years.


Comparative antigenic analysis of Mycobacterium avium complex (MAC) isolates from AIDS patients. Sonicates of several Mycobacterium avium complex (MAC) strains isolated from acquired immunodeficiency syndrome (AIDS) patients were characterized in order to study the prominent antigens of these strains. Sonicates of 6-week-old cultures were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. A major 12 kDa glycoprotein antigen was observed in all the sonicates along with other proteins ranging up to 100 kDa. Western blotting, using the 12 kDa M. leprae 'specific' murine monoclonal antibody (MAb) MLO6, indicated the presence of a determinant in the 12 kDa antigen (in all the MAC isolates studied) which was immunologically cross-reactive with the 12 kDa antigen of M. leprae. The transparent variant of MAC 101 also demonstrated MLO6 reactivity while the opaque variant did not. Polyclonal antiserum raised against MAC 101 sonicate reacted with all the MAC isolates in immunodiffusion. These observations point to the cross-reactivity between these strains and suggest that they possess a M. leprae 'specific' determinant on a cross-reacting component which could be involved in virulence.


Mycobacterial lymphadenitis in Western Australia. The records of 172 patients with culture-positive mycobacterial lymphadenitis in Western Australia between January 1972 and December 1989 inclusive have been reviewed. Of the 118 children under 7 years of age, the disease was caused by M. tuberculosis in 4%, the M. avium complex in 74% and M. scrofulaceum in 20%, whereas in the 54 adults aged 15 years and over, the same organisms were responsible for 89%, 2% and 4% respectively of their diseases. Tuberculous (TBC) lymphadenitis affected mainly adult Asian migrants (71%), while non-tuberculous mycobacterial (NTM) lymphadenitis predominantly affected non-Aboriginal Australian children (92%). The two conditions differed significantly in their distribution of disease in the lymph nodes (P < 0.001). Patients with the TBC disease had a longer (P < 0.001) duration of symptoms before diagnosis but less common (P < 0.02) local complications at presentation than those with the NTM disease. The response of TBC lymphadenitis to medical treatment was excellent with no failure or relapse in the 43 patients followed up to 12 months. Total excision was curative for NTM lymphadenitis although in 10% a second excision was needed because of relapse or residual disease. In a selected group of children, the double Mantoux test was shown to have a 79% sensitivity and a 69% specificity in the diagnosis of the NTM disease. Over the last decade, the prevalence of NTM lymphadenitis in Western Australia decreased while that of TBC lymphadenitis remained steady.


Lymph node tuberculosis: 7-year experience in Veterans General Hospital, Taipei, Taiwan. We retrospectively studied 71 cases of lymph node tuberculosis confirmed by culture or pathology from 1983 to 1989. Young adults were most frequently involved and the female to male ratio was 3:2. of 71 patients, three-quarters presented with palpable masses and two-thirds were asymptomatic. The cervical nodes were most frequently involved. Roentgenographic evidence of pulmonary tuberculosis was detected in 42% of patients and sputum culture-positive tuberculosis occurred in 7%. Tuberculin skin testing is less useful in our country due to routine BCG vaccination during infancy and early childhood. Selective excisional biopsy in addition to clinical information was necessary for differential diagnosis. 48 patients received regular treatment and were followed up for at least 1 year. Fresh nodes or enlargement of existing nodes developed in 10% of patients during treatment. Residual nodes were present in 10% of patients at the end of 9-month treatment with rifampicin, isoniazid and ethambutol, including prolonged or modified regimens in some individuals. In conclusion, in areas with a high frequency of tuberculous strains presenting a primary resistance to isoniazid, a 9-month regimen of rifampicin, isoniazid and ethambutol is recommended for lymph node tuberculosis.


Case-control study of the efficacy of BCG immunization against pulmonary tuberculosis in young adults in Santiago, Chile. We performed a case-control study of the efficacy of BCG immunization against pulmonary tuberculosis in 15- to 35-year-old Chilean patients born during a period when BCG coverage was incomplete. Our aims were to determine BCG efficacy against pulmonary tuberculosis in young adults, to determine if repeated BCG immunization increased its protective effect, and to determine factors that could explain the failure of BCG immunization in patients with tuberculosis. We studied 68 patients who had pulmonary tuberculosis based on positive AFB in at least 1 of 2 sputum smears, a positive confirmatory culture and compatible chest roentgenogram abnormalities. The control group were 188 individuals without pulmonary tuberculosis seeking medical care for other ailments. The percentage of non-immunized individuals was 13.2 among patients with tuberculosis and 12.2 among controls. The vaccine efficacy calculated from these data was 10%. There was no difference in the percentage of individuals with 1, 2 and 3 BCG scars between tuberculosis patients and controls. The number and percent of individuals exposed to tuberculosis among BCG-immunized and non-immunized tuberculosis patients and controls were similar. No significant differences between BCG-immunized and non-immunized individuals were detected in tuberculosis patients or in the control group. However, tuberculosis patients as a group had significantly lower weight, education level, employment rate and family income than controls. These observations suggest that the development of pulmonary tuberculosis in BCG-immunized young adults is favored by the presence of genetic and/or acquired predisposing factors capable of overriding protective immunity induced by BCG vaccination.


10-year assessment of treatment outcome among Cambodian refugees with sputum smear-positive tuberculosis in Khao-I-Dang, Thailand. Tuberculosis control among displaced persons is fraught with difficulties to ensure adherence of patients to treatment for a prolonged period of time. In the Khao-I-Dang camp for Cambodian refugees an approach with daily, directly observed treatment throughout the course of 6 months duration was chosen to address the problem. Of a total 929 patients with sputum smear-positive tuberculosis who were enrolled from 1981 to 1990, 5.0% died, 75.5% completed treatment and were bacteriologically cured with a day-to-day adherence of more than 98%, none failed bacteriologically, 19.2% were transferred to another camp where continuation of treatment was guaranteed, and only 0.4% absconded from treatment. These data suggest that the approach to tuberculosis control in this refugee camp was very effective in cutting the chain of transmission of tuberculosis in a highly mobile population and in reducing substantially unnecessary morbidity and mortality.


Human tuberculosis due to Mycobacterium bovis: report of 10 cases. During the period 1986-1990, 10 cases of human disease caused by Mycobacterium bovis were diagnosed in our hospital. The incidence, in relation to the cases of disease from Mycobacterium tuberculosis diagnosed in the same period, was 0.9%. The patients had an average age of 32 years (range 5-68 years). Pulmonary disease was observed in 5 patients (50%), lymphadenitis in 2, pleural effusion in 2 and peritoneal in 1. The most significant of the epidemiological features was that 2 patients were veterinary students. There was 1 death from ovarian neoplasia with abdominal dissemination. The other cases responded favourably to treatment with standard chemotherapy of 6-12 months achieving cure, without relapse, of all the patients.


Spinal infection by Mycobacterium xenopi in a non-immunosuppressed patient. A previously fit 77-year-old woman was found to have a paravertebral abscess. This was aspirated, yielding Mycobacterium xenopi, but no other pathogens. Antituberculosis chemotherapy with four first-line agents was commenced, with some response but continuing pain. Reports of extrapulmonary M. xenopi infections are rare. Most previous cases have involved immunosuppressed patients. This is the first reported case of spinal M. xenopi infection in a non-immunosuppressed patient, but radiological evidence suggests that previous tuberculous infection may have damaged the lumbar vertebrae, rendering them susceptible to infection by M. xenopi.


Another view to blood and body substance precaution: 1988-91. Occupational transmission of human immunodeficiency virus (HIV) in hospitals can be prevented with the use of 'blood and body substance precaution'. At the Royal Victoria Hospital, an infection control objective is to get employees automatically to use blood and body substance precaution with all patients--without relying on isolation signs. The concept of blood and body substance precaution was introduced in 1988 and simultaneously used with disease-specific signs. It was observed that disease-specific signs were mostly used to identify HIV-positive patients; this was verified under documented surveillance from July 7 to August 8, 1990, when 60 patients (14 HIV-positive and 46 whose HIV etiology was unknown) were observed. All 14 known HIV-positive patients were isolated with signs, while only four of 46 unknown HIV-positive patients (8.6%) had signs. The views of individual employees were subsequently studied via a questionnaire and results from this survey showed there was preference for isolating HIV-positive patients and identifying them with a sign.


Hospital outbreak traced to a case of Norwegian scabies. A hospital outbreak, traced to a case of Norwegian scabies, resulted in 45 and 32 symptomatic cases in staff and patients, respectively. A total of 228 asymptomatic in-patient contacts and over 500 staff required prophylactic treatment with either 1% gamma benzene hexachloride lotion or 5% permethrin cream. Recurrences occurred in seven staff members and five patients. The outbreak was contained within four months.


How to clean and maintain urinary leg bags: 'easy on the nose'. People with a dysfunctional bladder may have to wear a urinary collection bag. The authors found that the current practice of rinsing leg bags with water and cleaning them in the Cidamatic washer did not fully clean the bags. A trial of cleaning with Urolux showed that the bags were cleaner, smelled better and lasted longer, as well as that the procedure was easy and cost effective.


Results of CHICA-Canada survey of long term care infection control practitioners. Recognizing the unique and varied needs of infection control practitioners (ICPs) in long term care (LTC) facilities across Canada, CHICA-Canada established a task group to explore this area of practice and to determine the needs that could be met by CHICA-Canada. In March 1992 surveys were sent to CHICA-Canada members practicing in LTC facilities. Surveys were also sent to LTC associations in each province for distribution to their member agencies. A copy of the survey was published in The Canadian Journal of Infection Control in Summer 1992. As of August 31, 1992, 271 surveys have been returned from both members and nonmembers. The findings of the survey depict the special needs, unique practice settings and varied roles of ICPs in LTC facilities.


[Relationship between health services for maternal and child health and working hours of public health nurses]. Based on the "Maternal and Child Health Service Act", public health centers and municipalities offer health education, health counseling, health examination, and home visits for district children and for their mothers. The relationship between the number of the MCH services offered and the working hours of public health nurses at the public health centers and the municipalities was analyzed. Data were taken by a survey in 1989, which was used for evaluating services provided to the children and their mothers in 1988. Questionnaires were sent to 23 health centers and their districts and 100 responses from 8 wards, 20 cities, 47 towns, and 25 villages were analyzed. When total working hours of the public health nurse for MCH are allocated to the four parts-planning, implementation, evaluation and training-86.7% of working hours are for implementation itself. The correlation coefficient between the total working hours of the public health nurse for MCH and the population, and the number of births per year, were significantly positive. A total of 107 hours were supplied for the infant child health examination per 100 births per year, for which 64% was for implementation itself. In the case of the health examination for three-year-old children, total working hours were 143 hours, for with 79% was for implementation itself. The number of mother-child handbooks issued, the number of health education classes and health counselings conducted, various health examinations performed, and home visits made were correlated significantly with the working hours of the public health nurse.


[Structure of communication between physicians and patients from the viewpoint of community health]. Understanding the structure and problems of communication between physicians and patients should be achieved before introducing a medical information network system for community health. To this end a questionnaire survey was performed on 2,362 patients who saw physicians in medical facilities in a certain district of Hiroshima city. As a result, it was revealed that 'explanations given by doctors' and 'explanatory ability of patients' were mutually closely related and formed a basis for other aspects of communication and patient behavior. Satisfaction with the explanation given by physicians declined with examination time of less than 5 minutes and examination in hospitals rather than in clinics. Explanatory ability of patients decreased as age of patients increased and showed a remarkable decrease in patients of more than 80 years old. This suggested the existence of risk that information necessary for safe examinations may not be transmitted to physicians. These results pointed out the importance of a supporting system of communication especially for the elderly patient.


[Observation of sequential changes in results of oral glucose tolerance tests in individuals]. Using data from a series of health examination tests for members and their family of all agricultural cooperative associations in Hiroshima Prefecture during a fifteen year period from 1975 to 1989, sequential changes of the results of oral glucose tolerance tests in each year interval from 1 to 5 were studied for about 4300 individuals who participated in testing at least two times during the period. For those classified as normal on one test, the proportion of those who met the criteria of diabetes mellitus in 1 to 5 years later was less than one percent for both male and female. The changing rates from borderline or impaired glucose tolerance (IGT) to diabetes 1 to 5 years later were higher than the rates from normal to diabetes with the rate from borderline to diabetes one year later being 1.0 percent and IGT to diabetes 13.3 percent for males, and 0.8 percent and 6.4 percent respectively for females. The changing rates from non-diabetes to diabetes were higher for males than for females and were higher for the older age group than for the younger group. The rates from borderline and IGT to diabetes increased with longer interval but did not parallel the increase in time interval. For those classified as having diabetes on one test, the proportion of those classified as diabetic again in later years was around 60 percent and independent of length of interval years. From those results it appears that reporting the changing rate from non-diabetes to diabetes in one year by WHO diabetes criteria as the incidence of diabetes may be inappropriate.


[The prevalence of diabetes mellitus and impaired glucose tolerance studied by 75 gram oral glucose tolerance test in a rural island population]. A mass health examination was performed to assess the glucose tolerance of inhabitants of the island of Ojika, in the Goto islands, Nagasaki prefecture Japan. There were 554 males and 820 females older than 34 years who participated in the mass health examination, a response rates of 42 percent and 52 percent for males and females respectively. Serum glucose levels after overnight fasting and at 2 hours after a 75 gram oral glucose tolerance were used with WHO criteria to classify individuals. Among these subjects, the prevalence of diabetes mellitus increased with age, with a prevalence of diabetes mellitus of around 10 percent in the older subjects. The prevalence for males was higher than that for females. Prevalences of impaired glucose tolerance were roughly in the 15-25 percent range and did not show clear differences among different age groups and sexes. From a questionnaire survey of all island inhabitants, it was considered that the degree of bias of the results was small, if any. The true prevalence for all the inhabitants may be a little larger than the observed prevalence of these subjects.


[A survey of body temperatures in the elderly and the thermal environment in nursing homes]. In order to understand the relation between body temperatures and activities in the elderly, sublingual temperatures and activities of daily living (ADL) of 92 elderly people living in nursing homes were measured in the winter of 1989 and 1990. Thermal conditions in the three nursing homes were also measured simultaneously. In two nursing homes, where most of the people of low ADL lived, room temperatures were usually kept above 20 degrees C during most of the day, while in the remaining home, where many of the people of high ADL lived, room temperatures in the morning decreased to 8 degrees C. In spite of the better thermal conditions, mean sublingual temperatures, measured in the morning, of the low ADL group were significantly lower than that of middle and the high ADL groups. Moreover, the prevalence of low body temperatures (< 35.5 degrees C) was higher in the low ADL group than in the other two groups. From these results it appears that investigations of the living environment for older people should be widened.